细胞信号通路图大全
细胞信号通路大全
1PPAR信号通路：过氧化物酶体增殖物激活受体(PPARs)是与维甲酸、类固醇和甲状腺激素受体相关的配体激活转录因子超家族核激素受体成员。
它们作为脂肪传感器调节脂肪代谢酶的转录。
PPARs由PPARα、PPARβ和PPARγ3种亚型组成。
PPARα主要在脂肪酸代谢水平高的组织，如：肝、棕色脂肪、心、肾和骨骼肌表达。
他通过调控靶基因的表达而调节机体许多生理功能包括能量代谢、生长发育等。
另外，他还通过调节脂质代谢的生物感受器而调节细胞生长、分化与凋亡。
PPARa同时也是一种磷酸化蛋白，他受多种磷酸化酶的调节包括丝裂原激活蛋白激酶(ERK-和p38．MAPK)，蛋白激酶A和C(PKA，PKC)，AMPK和糖原合成酶一3(GSK3)等调控。
调控PPARa生长信号的酶报道有MAPK、PKA和GSK3。
PPARβ广泛表达于各种组织，而PPARγ主要局限表达在血和棕色脂肪，其他组织如骨骼肌和心肌有少量表达。
PPAR-γ在诸如炎症、动脉粥样硬化、胰岛素抵抗和糖代谢调节，以及肿瘤和肥胖等方面均有着举足轻重的作用，而其众多生物学效应则是通过启动或参与的复杂信号通路予以实现。
鉴于目前人们对PPAR—γ信号通路尚不甚清，PPARs通常是通过与9-cis维甲酸受体(RXR)结合实现其转录活性的。
2MAPK信号通路:mapk简介:丝裂原激活蛋白激酶（mitogen—activatedproteinkinase，MAPK）是广泛存在于动植物细胞中的一类丝氨酸/苏氨酸蛋白激酶。
作用主要是将细胞外刺激信号转导至细胞及其核内，并引起细胞的生物化学反应（增殖、分化、凋亡、应激等）。
MAPKs家族的亚族:ERKs（extracellularsignalregulatedkinase) ：包括ERK1、ERK2。
生长因子、细胞因子或激素激活此通路，介导细胞增殖、分化。
JNKs(c-JunN-terminalkinase)包括JNK1、JNK2、JNK3。
细胞信号通路大全
1 PPAR信号通路：过氧化物酶体增殖物激活受体( PPARs) 是与维甲酸、类固醇和甲状腺激素受体相关的配体激活转录因子超家族核激素受体成员。
它们作为脂肪传感器调节脂肪代谢酶的转录。
PPARs由PPARα、PPARβ和PPARγ 3种亚型组成。
PPARα主要在脂肪酸代谢水平高的组织，如：肝、棕色脂肪、心、肾和骨骼肌表达。
他通过调控靶基因的表达而调节机体许多生理功能包括能量代谢、生长发育等。
另外，他还通过调节脂质代谢的生物感受器而调节细胞生长、分化与凋亡。
PPARa同时也是一种磷酸化蛋白，他受多种磷酸化酶的调节包括丝裂原激活蛋白激酶( ERK-和p38．M APK) ，蛋白激酶A和C( PKA，PKC) ，AM PK和糖原合成酶一3( G SK3) 等调控。
调控PPARa生长信号的酶报道有M APK、PKA和G SK3。
PPARβ广泛表达于各种组织，而PPAR γ主要局限表达在血和棕色脂肪，其他组织如骨骼肌和心肌有少量表达。
PPAR-γ在诸如炎症、动脉粥样硬化、胰岛素抵抗和糖代谢调节，以及肿瘤和肥胖等方面均有着举足轻重的作用，而其众多生物学效应则是通过启动或参与的复杂信号通路予以实现。
鉴于目前人们对PPAR—γ信号通路尚不甚清，PPARs 通常是通过与9-cis维甲酸受体( RXR)结合实现其转录活性的。
2 MAPK信号通路:mapk简介:丝裂原激活蛋白激酶（mitogen—activated protein kinase，MAPK）是广泛存在于动植物细胞中的一类丝氨酸/苏氨酸蛋白激酶。
作用主要是将细胞外刺激信号转导至细胞及其核内，并引起细胞的生物化学反应（增殖、分化、凋亡、应激等）。
MAPKs家族的亚族 :ERKs（extracellular signal regulated kinase)：包括ERK1、ERK2。
生长因子、细胞因子或激素激活此通路，介导细胞增殖、分化。
JNKs(c-Jun N-terminal kinase)包括JNK1、JNK2、JNK3。
信号通路合辑
信号通路合辑纵观现如今的科研发展趋势，⽆论哪⽅⾯的研究都脱离不了分⼦机制，其实归根结底就是搞明⽩信号通路中上下游的基因是如何调控的，受到了哪些因素的影响。
华美⽣物特别整理了各研究领域信号通路⽰意图，以便于我们获取最直接的科研思路。
AMPK signaling pathway腺苷酸激活蛋⽩激酶 (AMPK) 在细胞能量稳态调节中起到关键作⽤。
在低⾎糖、低氧、缺⾎和热休克等情况下，可激活AMPK。
AMPK可作为异源三聚体复合体出现，内含⼀个催化性α亚单位和调节性β和γ亚单位。
AMP结合到γ亚单位后，可变构激活复合体，使其苏氨酸172位点更易磷酸化的底物，在α亚单位的激活环中更易被主要的上游AMPK激酶LKB1 磷酸化。
AMPK还能被CAMKK2在苏氨酸172位点直接磷酸化，这是由代谢激素（如脂联素和瘦素）刺激后胞内钙离⼦⽔平变化引起的反应。
作为细胞能量感受器，AMPK 可对ATP低⽔平做出反应，被激活后，可对补充细胞 ATP 供应的信号转导通路做出正向调控，这些通路包括脂肪酸氧化和⾃噬。
Apoptosis细胞凋亡，为⼀种细胞程序性死亡。
相对于细胞坏死（necrosis），细胞凋亡是细胞主动实施的。
细胞凋亡⼀般由⽣理或病理性因素引起。
⽽细胞坏死则主要为缺氧造成，两者可以很容易通过观察区分开来。
Caspase家族属于半胱氨酸蛋⽩酶。
起始组Caspase包括caspase-2,-8,-9,-10,-11和-12,与促凋亡信号紧密相连，⼀旦激活，这些酶会切割并激活下游的效应组Caspase，包括Caspase-3,-6,-7。
效应 Caspase通过对细胞内蛋⽩特定的天冬氨酸残基位置处进⾏切割实现细胞的凋亡。
FasL和 TNF对Fas和 TNFR的结合能够激活caspase-8和-10。
DNA损伤诱导PIDD的表达，PIDD与RAIDD 和caspase-2结合并激活caspase-2。
受损线粒体中释放的细胞⾊素C与caspase-9的活化相关。
干货细胞信号通路图解之免疫和炎症相关信号通路
⼲货细胞信号通路图解之免疫和炎症相关信号通路（1）Jak/Stat Signaling: IL-6 Receptor Family。
Jak和Stat是许多调节细胞⽣长、分化、存活和病原体抵抗信号通路中的关键部分。
就有这样⼀个通路涉及到IL-6（gp130）受体家族，它帮助调节B细胞的分化，浆细胞⽣成和急性期反应。
细胞因⼦结合引起受体的⼆聚化同时激活受体结合的Jak蛋⽩，活化的Jak蛋⽩对受体和⾃⾝进⾏磷酸化。
这些磷酸化的位点成为带有SH2结构的Stat蛋⽩和接头蛋⽩的结合位置，接头蛋⽩将受体和MAP激酶，PI3激酶/Akt还有其他的通路联系在⼀起。
受体结合的Stat蛋⽩被Jak磷酸化后形成⼆聚体，转移进⼊细胞核调节⽬的基因的表达。
细胞因⼦信号传导抑制分⼦（SOCS）家族的成员通过同源或异源的反馈减弱受体传递的信号。
Jak或Stat参与其他受体蛋⽩的信号传导，在下⾯Jak/Stat使⽤表格中有这⽅⾯的列举。
研究⼈员已经发现Stat3和Stat5在⼀些实体肿瘤中被酪氨酸激酶⽽不是Jaks组成性激活。
JAK/STAT途径介导细胞因⼦的效应，如促红细胞⽣成素，⾎⼩板⽣成素，G-CSF，这些细胞因⼦分别是⽤于治疗贫⾎，⾎⼩板减少症和中性粒细胞减少症的蛋⽩质类药物。
该途径也通过⼲扰素介导信号通路，⼲扰素可以⽤来作为抗病毒和抗增殖剂。
研究⼈员发现，失调的细胞因⼦信号有助于癌症的发⽣。
异常的IL-6的信号或导致⾃⾝免疫性疾病，炎症，癌症，如前列腺癌和多发性⾻髓瘤的发⽣。
Jak抑制剂⽬前正在多发性⾻髓瘤模型中进⾏测试。
Stat3具有潜在促癌性（原癌基因）,在许多癌症中持续的表达。
在⼀些癌细胞中，细胞因⼦信号传导和表⽪⽣长因⼦受体（EGFR）家族成员之间存在交流。
Jak激活突变是恶性⾎液病中主要的分⼦机制。
研究⼈员已经在Jak2假激酶域中发现⼀个特有的体细胞突变（V617F），这个突变常常发⽣于真性红细胞增多症，原发性⾎⼩板增多症和⾻髓纤维化症患者。
专题二 常见的细胞信号转导通路ppt课件
• JAK既能磷酸化与其相结合的细胞因子受体，又能磷酸 化多个含特定SH2结构域的信号分子。
• JAK蛋白家族共包括4个成 员：JAK1、JAK2、JAK3以 及Tyk2，它们在结构上有7 个JAK同源结构域（JH）。 JH1结构域为激酶区、JH2 结构域是“假”激酶区、 JH6和JH7是受体结合区域
JAK-STAT信号通路
• 最后，激酶JAK催化结合在受体上的STAT蛋白发 生磷酸化修饰，活化的STAT蛋白以二聚体的形式 进入细胞核内与靶基因结合，调控基因的转录。
• 一种JAK激酶可以参与多种细胞因子的信号转导过 程，一种细胞因子的信号通路也可以激活多个JAK 激酶，但细胞因子对激活的STAT分子却具有一定 的选择性。例如IL-4激活STAT6，而IL-12却特异性 激活STAT4。
JAK-STAT信号通路
• 细胞因子与相应的受体 结合后引起受体分子的 二聚化，这使得与受体 偶联的JAK激酶相互接 近并通过交互的酪氨酸 磷酸化作用而活化。
• JAK激活后催化受体上的酪氨酸残基发生磷酸化修饰， 继而这些磷酸化的酪氨酸位点与周围的氨基酸序列形 成“停泊位点”（docking site），同时含有SH2结构域 的STAT蛋白被招募到这个“停泊位点”。
专题二 常见的细胞信号通路
JAK-STAT TNFR-NF-KB Keap1-Nrf2
一、JAK-STAT信号通路
• JAK-STAT信号通路主要介导细胞因子（ IFNα/β，IFNγ, IL-10, IL-6等）和生长因子（ EPO, GH, EGF, PDGF）刺 激的信号转导通路，参与细胞的增殖、分化、凋亡以及 免疫调节等多种生物学过程。
细胞常见信号通路图片合集
目录actin肌丝 (5)Wnt/LRP6 信号 (7)WNT信号转导 (7)West Nile 西尼罗河病毒 (8)Vitamin C 维生素C在大脑中的作用 (10)视觉信号转导 (11)VEGF，低氧 (13)TSP-1诱导细胞凋亡 (15)Trka信号转导 (16)dbpb调节mRNA (17)CARM1甲基化 (19)CREB转录因子 (20)TPO信号通路 (21)Toll-Like 受体 (22)TNFR2 信号通路 (24)TNFR1信号通路 (25)IGF-1受体 (26)TNF/Stress相关信号 (27)共刺激信号 (29)Th1/Th2 细胞分化 (30)TGF beta 信号转导 (32)端粒、端粒酶与衰老 (33)TACI和BCMA调节B细胞免疫 (35)T辅助细胞的表面受体 (36)T细胞受体信号通路 (37)T细胞受体和CD3复合物 (38)Cardiolipin的合成 (40)Synaptic突触连接中的蛋白 (42)HSP在应激中的调节的作用 (43)Stat3 信号通路 (45)SREBP控制脂质合成 (46)酪氨酸激酶的调节 (48)Sonic Hedgehog (SHH)受体ptc1调节细胞周期 (51)Sonic Hedgehog (Shh) 信号 (53)SODD/TNFR1信号 (56)AKT/mTOR在骨骼肌肥大中的作用 (58)G蛋白信号转导 (59)IL1受体信号转导 (60)acetyl从线粒体到胞浆过程 (62)趋化因子chemokine在T细胞极化中的选择性表达 (63)SARS冠状病毒蛋白酶 (65)SARS冠状病毒蛋白酶 (67)Parkin在泛素-蛋白酶体中的作用 (69)nicotinic acetylcholine受体在凋亡中的作用 (71)线粒体在细胞凋亡中的作用 (73)MEF2D在T细胞凋亡中的作用 (74)Erk5和神经元生存 (75)ERBB2信号转导 (77)GPCRs调节EGF受体 (78)BRCA1调节肿瘤敏感性 (79)Rho细胞运动的信号 (81)Leptin能逆转胰岛素抵抗 (82)转录因子DREAM调节疼敏感 (84)PML调节转录 (86)p27调节细胞周期 (88)MAPK信号调节 (89)细胞因子调节造血细胞分化 (91)eIF4e和p70 S6激酶调节 (92)eIF2调节 (93)谷氨酸受体调节ck1/cdk5 (94)BAD磷酸化调节 (95)plk3在细胞周期中的作用 (96)Reelin信号通路 (97)RB肿瘤抑制和DNA破坏 (98)NK细胞介导的细胞毒作用 (99)Ras信号通路 (100)Rac 1细胞运动信号 (101)PTEN依赖的细胞生长抑制和细胞凋亡 (103)蛋白激酶A（PKA）在中心粒中的作用 (104)notch信号通路 (106)蛋白酶体Proteasome复合物 (108)Prion朊病毒的信号通路 (109)早老素Presenilin在notch和wnt信号中的作用 (110)淀粉样蛋白前体信号 (112)mRNA的poly(A)形成 (113)PKC抑制myosin磷酸化 (114)磷脂酶C（PLC）信号 (115)巨噬细胞Pertussis toxin不敏感的CCR5信号通路 (116)Pelp1调节雌激素受体的活性 (117)PDGF信号通路 (118)p53信号通路 (120)p38MAPK信号通路 (121)Nrf2是氧化应激基本表达的关键基因 (122)OX40信号通路 (123)hTert转录因子的调节作用 (124)hTerc转录调节活性图 (125)AIF在细胞凋亡中的作用 (126)Omega氧化通路 (127)核受体在脂质代谢和毒性中的作用 (129)NK细胞中NO2依赖的IL-12信号通路 (131)TOR信号通路 (133)NO信号通路 (134)NF-kB信号转导通路 (135)NFAT与心肌肥厚的示意图 (137)神经营养素及其表面分子 (139)神经肽VIP和PACAP防止活化T细胞凋亡图 (141)神经生长因子信号图 (142)细胞凋亡信号通路 (144)MAPK级联通路 (144)MAPK信号通路图 (145)BCR信号通路 (146)蛋白质乙酰化示意图 (147)wnt信号通路 (148)胰岛素受体信号通路 (149)细胞周期在G2/M期的调控机理图 (151)细胞周期G1/S检查点调控机理图 (152)Jak-STAT关系总表 (153)Jak/STAT 信号 (155)TGFbeta信号 (156)NFkappaB信号 (157)p38 MAPK信号通路 (159)SAPK/JNK 信号级联通路 (160)从G蛋白偶联受体到MAPK (161)MAPK pathwayMAPK级联信号图 (162)eIF-4E和p70 S6激酶调控蛋白质翻译 (163)eif2蛋白质翻译 (164)蛋白质翻译示意图 (165)线粒体凋亡通路 (167)死亡受体信号通路 (168)凋亡抑制通路 (170)细胞凋亡综合示意图 (171)Akt/Pkb信号通路 (172)MAPK/ERK信号通路 (174)哺乳动物MAPK信号通路 (175)Pitx2多步调节基因转录 (176)IGF-1R导致BAD磷酸化的多个凋亡路径 (177)多重耐药因子 (179)mTOR信号通路 (180)Msp/Ron受体信号通路 (181)单核细胞和其表面分子 (182)线粒体的肉毒碱转移酶（CPT）系统 (183)METS影响巨噬细胞的分化 (184)Anandamide，内源性大麻醇的代谢 (186)黑色素细胞（Melanocyte）发育和信号 (187)DNA甲基化导致转录抑制的机理图 (188)蛋白质的核输入信号图 (190)PPARa调节过氧化物酶体的增殖 (192)对乙氨基酚（Acetaminophen）的活性和毒性机理 (194)mCalpain在细胞运动中的作用 (196)MAPK信号图 (198)MAPK抑制SMRT活化 (200)苹果酸和天门冬酸间的转化 (201)低密度脂蛋白（LDL）在动脉粥样硬化中的作用 (202)LIS1基因在神经细胞的发育和迁移中的作用图 (204)Pyk2与Mapk相连的信号通路 (205)galactose代谢通路 (206)Lectin诱导补体的通路 (207)Lck和Fyn在TCR活化中的作用 (208)乳酸合成图 (209)Keratinocyte分化图 (210)离子通道在心血管内皮细胞中的作用 (211)离子通道和佛波脂（Phorbal Esters）信号 (213)内源性Prothrombin激活通路 (214)Ribosome内化通路 (216)整合素（Integrin）信号通路 (217)胰岛素（Insulin）信号通路 (218)Matrix Metalloproteinases (219)组氨酸去乙酰化抑制剂抑制Huntington病 (220)Gleevec诱导细胞增殖 (222)Ras和Rho在细胞周期的G1/S转换中的作用 (224)DR3，4，5受体诱导细胞凋亡 (225)AKT调控Gsk3图 (226)IL-7信号转导 (227)IL22可溶性受体信号转导图 (229)IL-2活化T细胞图 (230)IL12和Stat4依赖的TH1细胞发育信号通路 (232)IL-10信号通路 (233)IL 6信号通路 (234)IL 5信号通路 (236)actin肌丝Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works.Activation by Wave-1, another member of the WASP family, also induces actinalterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, the Wiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function.Cory GO, Ridley AJ. Cell motility: braking WAVEs. Nature. 2002 Aug15;418(6899):732-3. No abstract available.Eden, S., et al. (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899), 790-3Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood. 2002 Sep 15;100(6):2113-22.Kreishman-Deitrick M, Rosen MK, Kreishman-Deltrick M. Ignition of a cellular machine. Nat Cell Biol. 2002 Feb;4(2):E31-3. No abstract available.Machesky, L.M., Insall, R.H. (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8(25), 1347-56Robinson, R.C. et al. (2001) Crystal structure of Arp2/3 complex. Science 294(5547), 1679-84Weeds A, Yeoh S. Structure. Action at the Y-branch. Science. 2001 Nov23;294(5547):1660-1. No abstract available.Wnt/LRP6 信号Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signalingWNT信号转导West Nile 西尼罗河病毒West Nile virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, Kunjin virus, yellow fever virus, Dengue virus, and Japanese encephalitis virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. WNV has rapidly spread across the United States through its insect host and causes neurological symptoms and encephalitis, which can result in paralysis or death. Since 1999 about 3700 cases of West Nile virus (WNV) infection and 200 deaths have been recorded in United States. The viral capsid protein likely contributes to theWNV-associated deadly inflammation via apoptosis induced through the mitochondrial pathway.WNV particles (50 nm in diameter) consist of a dense core (viral protein C encapsidated virus RNA genome) surrounded by a membrane envelope (viral E and M proteins embedded in a lipid bilayer). The virus binds to a specific cell surface protein (not yet identified), an interaction thought to involve E protein with highly sulfated neperan sulfate (HSHS) residues that are present on the surfaces of many cells and enters the cell by a process similar to that of endocytosis. Once inside the cell, the genome RNA is released into the cytoplasm via endosomal release, a fusion process involving acidic pH induced conformation change in the E protein. The RNA genome serves as mRNA and is translated by ribosomes into ten mature viral proteins are produced via proteolytic cleavage, which include three structural components and seven different nonstructural components of the virus. These proteins assemble and transcribe complimentary minus strand RNAs from the genomic RNA. The complimentary minus strand RNA in turns serves as template for the synthesis of positive-stranded genomic RNAs. Once viral E, preM and C proteins have accumulated to sufficient level, they assemble with the genomic RNA to form progeny virions, which migrate to the cell surface where they are surrounded with lipid envelop and released.Vitamin C 维生素C在大脑中的作用Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes that post-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import ofdietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles. Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1. Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.视觉信号转导The signal transduction cascade responsible for sensing light in vertebrates is one of the best studied signal transduction processes, and is initiated by rhodopsin in rodcells, a member of the G-protein coupled receptor gene family. Rhodopsin remains the only GPCR whose structure has been resolved at high resolution. Rhodopsin in the discs of rod cells contains a bound 11-cis retinal chromophore, a small molecule derived from Vitamin A that acts as the light sensitive portion of the receptor molecule, absorbing light to initiate the signal transduction cascade. When light strikes 11-cis retinal and is absorbed, it isomerizes to all-trans retinal, changing the shape of the molecule and the receptor it is bound to. This change in rhodopsin抯shape alters its interaction with transducin, the member of the G-protein gene family that is specific in its role in visual signal transduction. Activation of transducin causes its alpha subunit to dissociate from the trimer and exchange bound GDP for GTP, activating in turn a membrane-bound cyclic-GMP specific phosphodiesterase that hydrolyzes cGMP. In the resting rod cell, high levels of cGMP associate with a cyclic-GMP gated sodium channel in the plasma membrane, keeping the channels open and the membrane of the resting rod cells depolarized. This is distinct from synaptic generation of action potentials, in which stimulation induces opening of sodium channels and depolarization. When cGMP gated channels in rod cells open, both sodium and calcium ions enter the cell, hyperpolarizing the membrane and initiating the electrochemical impulse responsible for conveying the signal from the sensory neuron to the CNS. The rod cell in the resting state releases high levels of the inhibitory neurotransmitter glutamate, while the release of glutamate is repressed by the hyperpolarization in the presence of light to trigger a downstream action potential by ganglion cells that convey signals to the brain. The calcium which enters the cell also activates GCAP, which activates guanylate cyclase (GC-1 and GC-2) to rapidly produce more cGMP, ending the hyperpolarization and returning the cell to its resting depolarized state. A protein called recoverin helps mediate the inactivation of the signal transduction cascade, returning rhodopsin to its preactivated state, along with the rhodopsin kinase Grk1. Phosphorylation of rhodopsin by Grkl causes arrestin to bind, helping to terminate the receptor activation signal. Dissociation and reassociation of retinal, dephosphorylation of rhodopsin and release of arrestin all return rhodopsin to its ready state, prepared once again to respond to light.VEGF，低氧Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significantsimilarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA.. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.TSP-1诱导细胞凋亡As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.Trka信号转导Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkA through association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation.dbpb调节mRNAEndothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation.RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway.CARM1甲基化Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known.CREB转录因子The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively.TPO信号通路Thrombopoietin (TPO) binds to its receptor inducing aggregation and activation. TPO signals its growth regulating effects to the cell through several major pathways including MAPK (ERK and JNK), Protein Kinase C, and JAK/Stat.Toll-Like 受体The innate immune response responds in a general manner to factors present in invading pathogens. Bacterial factors such as lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, peptidoglycans and also CpG nucleic acids activate innate immunity as well as stimulating the antigen-specific immune response and triggering the inflammatory response. Members of the toll-like receptor (TLR) gene family convey signals stimulated by these factors, activating signal transduction pathways that result in transcriptional regulation and stimulate immune function. TLR2 is activated by bacterial lipoproteins, TLR4 is activated by LPS, and TLR9 is activated by CpG DNA; peptidoglycan recognition protein (PGRP) is activated bypeptidoglycan (PGN). The downstream signaling pathways used by these receptors are similar to that used by the IL-1 receptor, activating the IL-1 receptor associated kinase (IRAK) through the MyD88 adaptor protein, and signaling through TRAF-6 and protein kinase cascades to activate NF-kB and Jun. NF-kB and c-Jun activate transcription of genes such as the proinflammatory cytokines IL-1 and IL-12. Several recent reports have suggested that the functional outcomes of signaling via TLR2, TLR4 and PGRP are not equivalent. For example, while the LPS-induced,p38-dependent response was dependent upon PU.1 binding, the PGN-induced, p38 response was not. The intracelular receptor for PGN, PGRP is conserved from insects to mammals. In insects, PGRP activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown. However, it was suggested that an identical protein Tag7 was a tumor necrosis factor-like (TNF-like) cytokine.PGRP/Tag7 possesses cytotoxicity and triggers intranucleosomal DNA fragmentation in target cells in the same way as many known members of the TNF family. Fragmentation of DNA is one of the characteristics of apoptosis. The possibility that in another system, PGRP/Tag7 would induce NF-kB activation, as observed for TRAIL (TNF-related apoptosis-inducing ligand) receptors canot be ruled out.TNFR2 is the receptor for the 171 amino acid 19 kD TNF(beta) (a.k.a. lymphotoxin). TNF(beta) is produced by activated lymphocytes and can be cytotoxic to many tumor and other cells. In neutrophils, endothelial cells and osteoclasts TNF(beta) can lead to activation while in many other cell types it can lead to increased expression of MHC and adhesion molecules.TNFR1 (a.k.a. p55, CD120a) is the receptor for TNF(alpha) and also will bind TNF(beta). Upon binding TNF(alpha) a TNFR1+ cell is triggered to undergo apoptosis. This critical regulatory process is accomplished by activating the proteolytic caspase cascade that results in the degradation of many critical cellular proteinsIGF-1受体TNF/Stress相关信号TNF acts on several different signaling pathways through two cell surface receptors, TNFR1 and TNFR2 (See TNFR1 and TNFR2 Signaling Pathways) to regulate apoptotic pathways, NF-kB activation of inflammation, and activate stress-activated protein kinases (SAPKs). Interaction of TNFR1 with TRADD leads to activation of NF-kB and apoptosis pathways, while interaction with TRAF2 has generally been thought to be involved in stress kinase and NF-kB activation but is not required for TNF to induce apoptosis. Activation of NF-kB is mediated by TRAF2 through the NIK kinase and also by RIP but the observation that TNF activates NF-kB in mice lacking TRAF2 indicates that TRAF-2 does not play an essential role in this process. Stress-activated protein kinases, also called JNKs, are a family of map kinases activated by cellular stress and inflammatory signals. Binding of TNF to the TNFR1 receptor activates the germinal center kinase (GCK) through the TNF adaptor Traf2, activating the map kinase MEKK1. Both GCK and MEKK1 interact with Traf2, andGCK is required for MEKK1 activation by TNF, but GCK kinase activity does not appear to be required for MEKK1 activation. Instead, GCK activates MEKK1 by causing MEKK1 oligomerization and autophosphorylation. Tank increases the affinity of Traf2 for GCK to increase Map kinase activation by TNF. Once activated, MEKK1 stands at the top of a map kinase pathways leading to transcriptional regulation, including JNK phosphorylation of c-Jun to stimulate transcriptional activation by AP-1, a heterodimer of c-jun and fos or ATF proteins. The activation of the p38 Map kinase also contributes to AP-1 activation leading to the transcriptional activation of many stress and growth related genes. RIP has been suggested as a component of the p38 pathway in addition to playing a role in NF-kB activation. MEKK1 knockout mice support the role of MEKK1 in JNK activation in some cells but did not support MEKK1 dependent activation of NF-kB. Alternative redundant mechanisms may obscure the role of MEKK1 in NF-kB mechanisms. TNF activation of stress kinase pathways and downstream transcription factors may help to modulate the apoptotic pathways also activated by TNF.共刺激信号For a T cell to be activated by a specific antigen, the T cell receptor must recognize complexes of MHCI with the antigen on the surface of an antigen-presenting cell. T cells and the T cell receptor complex do not respond to antigen in solution, but even for the specific antigen they only respond to antigen-MHC-1 complexes on the cell surface. This interaction is necessary for T cell activation, but it is not sufficient. T cell activation also requires a co-stimulatory signal involving interaction of CD28 on the T cell with CD80 or CD86 (B7 family genes) on the antigen-presenting cell.CD28 activates a signal transduction pathway acting through PI-3K, Lck andGrb-2/ITK to provide its co-stimulatory signal for T cell activation. Another means to control T cell activation is by expressing factors that down-regulate T cell activation. Signaling by activated T cell receptors induces expression of CTLA-4, a receptor that opposes T cell activation. CTLA-4 has a higher affinity than CD28 for B7 proteins, terminating T cell activation. ICOS is a protein related to CD28 that is only expressed on activated T cells, and that provides another important co-stimulatory signal. The requirement for co-stimulatory signals provides additional control mechanisms that prevent inappropriate and hazardous T cell activation.。
细胞常见信号通路图片合集Word版
目录actin肌丝 (5)Wnt/LRP6 信号 (7)WNT信号转导 (7)West Nile 西尼罗河病毒 (8)Vitamin C 维生素C在大脑中的作用 (10)视觉信号转导 (11)VEGF，低氧 (13)TSP-1诱导细胞凋亡 (15)Trka信号转导 (16)dbpb调节mRNA (17)CARM1甲基化 (19)CREB转录因子 (20)TPO信号通路 (21)Toll-Like 受体 (22)TNFR2 信号通路 (24)TNFR1信号通路 (25)IGF-1受体 (26)TNF/Stress相关信号 (27)共刺激信号 (29)Th1/Th2 细胞分化 (30)TGF beta 信号转导 (32)端粒、端粒酶与衰老 (33)TACI和BCMA调节B细胞免疫 (35)T辅助细胞的表面受体 (36)T细胞受体信号通路 (37)T细胞受体和CD3复合物 (38)Cardiolipin的合成 (40)Synaptic突触连接中的蛋白 (42)HSP在应激中的调节的作用 (43)Stat3 信号通路 (45)SREBP控制脂质合成 (46)酪氨酸激酶的调节 (48)Sonic Hedgehog (SHH)受体ptc1调节细胞周期 (51)Sonic Hedgehog (Shh) 信号 (53)SODD/TNFR1信号 (56)AKT/mTOR在骨骼肌肥大中的作用 (58)G蛋白信号转导 (59)IL1受体信号转导 (60)acetyl从线粒体到胞浆过程 (62)趋化因子chemokine在T细胞极化中的选择性表达 (63)SARS冠状病毒蛋白酶 (65)SARS冠状病毒蛋白酶 (67)Parkin在泛素-蛋白酶体中的作用 (69)nicotinic acetylcholine受体在凋亡中的作用 (71)线粒体在细胞凋亡中的作用 (73)MEF2D在T细胞凋亡中的作用 (74)Erk5和神经元生存 (75)ERBB2信号转导 (77)GPCRs调节EGF受体 (78)BRCA1调节肿瘤敏感性 (79)Rho细胞运动的信号 (81)Leptin能逆转胰岛素抵抗 (82)转录因子DREAM调节疼敏感 (84)PML调节转录 (86)p27调节细胞周期 (88)MAPK信号调节 (89)细胞因子调节造血细胞分化 (91)eIF4e和p70 S6激酶调节 (92)eIF2调节 (93)谷氨酸受体调节ck1/cdk5 (94)BAD磷酸化调节 (95)plk3在细胞周期中的作用 (96)Reelin信号通路 (97)RB肿瘤抑制和DNA破坏 (98)NK细胞介导的细胞毒作用 (99)Ras信号通路 (100)Rac 1细胞运动信号 (101)PTEN依赖的细胞生长抑制和细胞凋亡 (103)蛋白激酶A（PKA）在中心粒中的作用 (104)notch信号通路 (106)蛋白酶体Proteasome复合物 (108)Prion朊病毒的信号通路 (109)早老素Presenilin在notch和wnt信号中的作用 (110)淀粉样蛋白前体信号 (112)mRNA的poly(A)形成 (113)PKC抑制myosin磷酸化 (114)磷脂酶C（PLC）信号 (115)巨噬细胞Pertussis toxin不敏感的CCR5信号通路 (116)Pelp1调节雌激素受体的活性 (117)PDGF信号通路 (118)p53信号通路 (120)p38MAPK信号通路 (121)Nrf2是氧化应激基本表达的关键基因 (122)OX40信号通路 (123)hTert转录因子的调节作用 (124)hTerc转录调节活性图 (125)AIF在细胞凋亡中的作用 (126)Omega氧化通路 (127)核受体在脂质代谢和毒性中的作用 (129)NK细胞中NO2依赖的IL-12信号通路 (131)TOR信号通路 (133)NO信号通路 (134)NF-kB信号转导通路 (135)NFAT与心肌肥厚的示意图 (137)神经营养素及其表面分子 (139)神经肽VIP和PACAP防止活化T细胞凋亡图 (141)神经生长因子信号图 (142)细胞凋亡信号通路 (144)MAPK级联通路 (144)MAPK信号通路图 (145)BCR信号通路 (146)蛋白质乙酰化示意图 (147)wnt信号通路 (148)胰岛素受体信号通路 (149)细胞周期在G2/M期的调控机理图 (151)细胞周期G1/S检查点调控机理图 (152)Jak-STAT关系总表 (153)Jak/STA T 信号 (155)TGFbeta信号 (156)NFkappaB信号 (157)p38 MAPK信号通路 (159)SAPK/JNK 信号级联通路 (160)从G蛋白偶联受体到MAPK (161)MAPK pathwayMAPK级联信号图 (162)eIF-4E和p70 S6激酶调控蛋白质翻译 (163)eif2蛋白质翻译 (164)蛋白质翻译示意图 (165)线粒体凋亡通路 (167)死亡受体信号通路 (168)凋亡抑制通路 (170)细胞凋亡综合示意图 (171)Akt/Pkb信号通路 (172)MAPK/ERK信号通路 (174)哺乳动物MAPK信号通路 (175)Pitx2多步调节基因转录 (176)IGF-1R导致BAD磷酸化的多个凋亡路径 (177)多重耐药因子 (179)mTOR信号通路 (180)Msp/Ron受体信号通路 (181)单核细胞和其表面分子 (182)线粒体的肉毒碱转移酶（CPT）系统 (183)METS影响巨噬细胞的分化 (184)Anandamide，内源性大麻醇的代谢 (186)黑色素细胞（Melanocyte）发育和信号 (187)DNA甲基化导致转录抑制的机理图 (188)蛋白质的核输入信号图 (190)PPARa调节过氧化物酶体的增殖 (192)对乙氨基酚（Acetaminophen）的活性和毒性机理 (194)mCalpain在细胞运动中的作用 (196)MAPK信号图 (198)MAPK抑制SMRT活化 (200)苹果酸和天门冬酸间的转化 (201)低密度脂蛋白（LDL）在动脉粥样硬化中的作用 (202)LIS1基因在神经细胞的发育和迁移中的作用图 (204)Pyk2与Mapk相连的信号通路 (205)galactose代谢通路 (206)Lectin诱导补体的通路 (207)Lck和Fyn在TCR活化中的作用 (208)乳酸合成图 (209)Keratinocyte分化图 (210)离子通道在心血管内皮细胞中的作用 (211)离子通道和佛波脂（Phorbal Esters）信号 (213)内源性Prothrombin激活通路 (214)Ribosome内化通路 (216)整合素（Integrin）信号通路 (217)胰岛素（Insulin）信号通路 (218)Matrix Metalloproteinases (219)组氨酸去乙酰化抑制剂抑制Huntington病 (220)Gleevec诱导细胞增殖 (222)Ras和Rho在细胞周期的G1/S转换中的作用 (224)DR3，4，5受体诱导细胞凋亡 (225)AKT调控Gsk3图 (226)IL-7信号转导 (227)IL22可溶性受体信号转导图 (229)IL-2活化T细胞图 (230)IL12和Stat4依赖的TH1细胞发育信号通路 (232)IL-10信号通路 (233)IL 6信号通路 (234)IL 5信号通路 (236)actin肌丝Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works.Activation by Wave-1, another member of the WASP family, also induces actinalterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, the Wiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function.Cory GO, Ridley AJ. Cell motility: braking WAVEs. Nature. 2002 Aug15;418(6899):732-3. No abstract available.Eden, S., et al. (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899), 790-3Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood. 2002 Sep 15;100(6):2113-22.Kreishman-Deitrick M, Rosen MK, Kreishman-Deltrick M. Ignition of a cellular machine. Nat Cell Biol. 2002 Feb;4(2):E31-3. No abstract available.Machesky, L.M., Insall, R.H. (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8(25), 1347-56Robinson, R.C. et al. (2001) Crystal structure of Arp2/3 complex. Science 294(5547), 1679-84Weeds A, Yeoh S. Structure. Action at the Y-branch. Science. 2001 Nov23;294(5547):1660-1. No abstract available.Wnt/LRP6 信号Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signalingWNT信号转导West Nile 西尼罗河病毒West Nile virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, Kunjin virus, yellow fever virus, Dengue virus, and Japanese encephalitis virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. WNV has rapidly spread across the United States through its insect host and causes neurological symptoms and encephalitis, which can result in paralysis or death. Since 1999 about 3700 cases of West Nile virus (WNV) infection and 200 deaths have been recorded in United States. The viral capsid protein likely contributes to theWNV-associated deadly inflammation via apoptosis induced through the mitochondrial pathway.WNV particles (50 nm in diameter) consist of a dense core (viral protein C encapsidated virus RNA genome) surrounded by a membrane envelope (viral E and M proteins embedded in a lipid bilayer). The virus binds to a specific cell surface protein (not yet identified), an interaction thought to involve E protein with highly sulfated neperan sulfate (HSHS) residues that are present on the surfaces of many cells and enters the cell by a process similar to that of endocytosis. Once inside the cell, the genome RNA is released into the cytoplasm via endosomal release, a fusion process involving acidic pH induced conformation change in the E protein. The RNA genome serves as mRNA and is translated by ribosomes into ten mature viral proteins are produced via proteolytic cleavage, which include three structural components and seven different nonstructural components of the virus. These proteins assemble and transcribe complimentary minus strand RNAs from the genomic RNA. The complimentary minus strand RNA in turns serves as template for the synthesis of positive-stranded genomic RNAs. Once viral E, preM and C proteins have accumulated to sufficient level, they assemble with the genomic RNA to form progeny virions, which migrate to the cell surface where they are surrounded with lipid envelop and released.Vitamin C 维生素C在大脑中的作用Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes that post-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import ofdietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles. Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1. Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.视觉信号转导The signal transduction cascade responsible for sensing light in vertebrates is one of the best studied signal transduction processes, and is initiated by rhodopsin in rod cells, a member of the G-protein coupled receptor gene family. Rhodopsin remains the only GPCR whose structure has been resolved at high resolution. Rhodopsin in the discs of rod cells contains a bound 11-cis retinal chromophore, a small molecule derived from Vitamin A that acts as the light sensitive portion of the receptor molecule, absorbing light to initiate the signal transduction cascade. When light strikes 11-cis retinal and is absorbed, it isomerizes to all-trans retinal, changing the shape of the molecule and the receptor it is bound to. This change in rhodopsin抯shape alters its interaction with transducin, the member of the G-protein gene family that is specific in its role in visual signal transduction. Activation of transducin causes its alpha subunit to dissociate from the trimer and exchange bound GDP for GTP, activating in turn a membrane-bound cyclic-GMP specific phosphodiesterase thathydrolyzes cGMP. In the resting rod cell, high levels of cGMP associate with a cyclic-GMP gated sodium channel in the plasma membrane, keeping the channels open and the membrane of the resting rod cells depolarized. This is distinct from synaptic generation of action potentials, in which stimulation induces opening of sodium channels and depolarization. When cGMP gated channels in rod cells open, both sodium and calcium ions enter the cell, hyperpolarizing the membrane and initiating the electrochemical impulse responsible for conveying the signal from the sensory neuron to the CNS. The rod cell in the resting state releases high levels of the inhibitory neurotransmitter glutamate, while the release of glutamate is repressed by the hyperpolarization in the presence of light to trigger a downstream action potential by ganglion cells that convey signals to the brain. The calcium which enters the cell also activates GCAP, which activates guanylate cyclase (GC-1 and GC-2) to rapidly produce more cGMP, ending the hyperpolarization and returning the cell to its resting depolarized state. A protein called recoverin helps mediate the inactivation of the signal transduction cascade, returning rhodopsin to its preactivated state, along with the rhodopsin kinase Grk1. Phosphorylation of rhodopsin by Grkl causes arrestin to bind, helping to terminate the receptor activation signal. Dissociation and reassociation of retinal, dephosphorylation of rhodopsin and release of arrestin all return rhodopsin to its ready state, prepared once again to respond to light.VEGF，低氧Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nucleartranslocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA.. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.TSP-1诱导细胞凋亡As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.Trka信号转导Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkA through association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation.dbpb调节mRNAEndothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation.RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway.CARM1甲基化Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known.CREB转录因子The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively.TPO信号通路Thrombopoietin (TPO) binds to its receptor inducing aggregation and activation. TPO signals its growth regulating effects to the cell through several major pathways including MAPK (ERK and JNK), Protein Kinase C, and JAK/Stat.Toll-Like 受体The innate immune response responds in a general manner to factors present in invading pathogens. Bacterial factors such as lipopolysaccharides (LPS, endotoxin), bacterial lipoproteins, peptidoglycans and also CpG nucleic acids activate innate immunity as well as stimulating the antigen-specific immune response and triggering the inflammatory response. Members of the toll-like receptor (TLR) gene family convey signals stimulated by these factors, activating signal transduction pathways that result in transcriptional regulation and stimulate immune function. TLR2 is activated by bacterial lipoproteins, TLR4 is activated by LPS, and TLR9 is activated by CpG DNA; peptidoglycan recognition protein (PGRP) is activated bypeptidoglycan (PGN). The downstream signaling pathways used by these receptors are similar to that used by the IL-1 receptor, activating the IL-1 receptor associated kinase (IRAK) through the MyD88 adaptor protein, and signaling through TRAF-6 and protein kinase cascades to activate NF-kB and Jun. NF-kB and c-Jun activate transcription of genes such as the proinflammatory cytokines IL-1 and IL-12. Several recent reports have suggested that the functional outcomes of signaling via TLR2, TLR4 and PGRP are not equivalent. For example, while the LPS-induced,p38-dependent response was dependent upon PU.1 binding, the PGN-induced, p38 response was not. The intracelular receptor for PGN, PGRP is conserved from insects to mammals. In insects, PGRP activates prophenoloxidase cascade, a part of the insect antimicrobial defense system. Because mammals do not have the prophenoloxidase cascade, its function in mammals is unknown. However, it was suggested that an identical protein Tag7 was a tumor necrosis factor-like (TNF-like) cytokine.PGRP/Tag7 possesses cytotoxicity and triggers intranucleosomal DNA fragmentation in target cells in the same way as many known members of the TNF family. Fragmentation of DNA is one of the characteristics of apoptosis. The possibility that in another system, PGRP/Tag7 would induce NF-kB activation, as observed for TRAIL (TNF-related apoptosis-inducing ligand) receptors canot be ruled out.TNFR2 信号通路TNFR2 is the receptor for the 171 amino acid 19 kD TNF(beta) (a.k.a. lymphotoxin). TNF(beta) is produced by activated lymphocytes and can be cytotoxic to many tumor and other cells. In neutrophils, endothelial cells and osteoclasts TNF(beta) can lead to activation while in many other cell types it can lead to increased expression of MHC and adhesion molecules.TNFR1信号通路TNFR1 (a.k.a. p55, CD120a) is the receptor for TNF(alpha) and also will bind TNF(beta). Upon binding TNF(alpha) a TNFR1+ cell is triggered to undergo apoptosis. This critical regulatory process is accomplished by activating the proteolytic caspase cascade that results in the degradation of many critical cellular proteinsIGF-1受体TNF/Stress相关信号TNF acts on several different signaling pathways through two cell surface receptors, TNFR1 and TNFR2 (See TNFR1 and TNFR2 Signaling Pathways) to regulate apoptotic pathways, NF-kB activation of inflammation, and activate stress-activated protein kinases (SAPKs). Interaction of TNFR1 with TRADD leads to activation of NF-kB and apoptosis pathways, while interaction with TRAF2 has generally been thought to be involved in stress kinase and NF-kB activation but is not required for TNF to induce apoptosis. Activation of NF-kB is mediated by TRAF2 through the NIK kinase and also by RIP but the observation that TNF activates NF-kB in mice lacking TRAF2 indicates that TRAF-2 does not play an essential role in this process. Stress-activated protein kinases, also called JNKs, are a family of map kinases activated by cellular stress and inflammatory signals. Binding of TNF to the TNFR1 receptor activates the germinal center kinase (GCK) through the TNF adaptor Traf2, activating the map kinase MEKK1. Both GCK and MEKK1 interact with Traf2, andGCK is required for MEKK1 activation by TNF, but GCK kinase activity does not appear to be required for MEKK1 activation. Instead, GCK activates MEKK1 by causing MEKK1 oligomerization and autophosphorylation. Tank increases the affinity of Traf2 for GCK to increase Map kinase activation by TNF. Once activated, MEKK1 stands at the top of a map kinase pathways leading to transcriptional regulation, including JNK phosphorylation of c-Jun to stimulate transcriptional activation by AP-1, a heterodimer of c-jun and fos or ATF proteins. The activation of the p38 Map kinase also contributes to AP-1 activation leading to the transcriptional activation of many stress and growth related genes. RIP has been suggested as a component of the p38 pathway in addition to playing a role in NF-kB activation. MEKK1 knockout mice support the role of MEKK1 in JNK activation in some cells but did not support MEKK1 dependent activation of NF-kB. Alternative redundant mechanisms may obscure the role of MEKK1 inNF-kB mechanisms. TNF activation of stress kinase pathways and downstream transcription factors may help to modulate the apoptotic pathways also activated by TNF.共刺激信号For a T cell to be activated by a specific antigen, the T cell receptor must recognize complexes of MHCI with the antigen on the surface of an antigen-presenting cell. T cells and the T cell receptor complex do not respond to antigen in solution, but even for the specific antigen they only respond to antigen-MHC-1 complexes on the cell surface. This interaction is necessary for T cell activation, but it is not sufficient. T cell activation also requires a co-stimulatory signal involving interaction of CD28 on the T cell with CD80 or CD86 (B7 family genes) on the antigen-presenting cell.CD28 activates a signal transduction pathway acting through PI-3K, Lck andGrb-2/ITK to provide its co-stimulatory signal for T cell activation. Another means to control T cell activation is by expressing factors that down-regulate T cell activation. Signaling by activated T cell receptors induces expression of CTLA-4, a receptor that opposes T cell activation. CTLA-4 has a higher affinity than CD28 for B7 proteins, terminating T cell activation. ICOS is a protein related to CD28 that is only expressed on activated T cells, and that provides another important co-stimulatory signal. The requirement for co-stimulatory signals provides additional control mechanisms that prevent inappropriate and hazardous T cell activation.。
细胞信号通路大全.pdf
1 PPAR信号通路：过氧化物酶体增殖物激活受体( PPARs) 是与维甲酸、类固醇和甲状腺激素受体相关的配体激活转录因子超家族核激素受体成员。
它们作为脂肪传感器调节脂肪代谢酶的转录。
PPARs由PPARα、PPARβ和PPARγ 3种亚型组成。
PPARα主要在脂肪酸代谢水平高的组织，如：肝、棕色脂肪、心、肾和骨骼肌表达。
他通过调控靶基因的表达而调节机体许多生理功能包括能量代谢、生长发育等。
另外，他还通过调节脂质代谢的生物感受器而调节细胞生长、分化与凋亡。
PPARa同时也是一种磷酸化蛋白，他受多种磷酸化酶的调节包括丝裂原激活蛋白激酶( ERK-和p38．M APK) ，蛋白激酶A和C( PKA，PKC) ，AM PK和糖原合成酶一3( G SK3) 等调控。
调控PPARa生长信号的酶报道有M APK、PKA和G SK3。
PPARβ广泛表达于各种组织，而PPAR γ主要局限表达在血和棕色脂肪，其他组织如骨骼肌和心肌有少量表达。
PPAR-γ在诸如炎症、动脉粥样硬化、胰岛素抵抗和糖代谢调节，以及肿瘤和肥胖等方面均有着举足轻重的作用，而其众多生物学效应则是通过启动或参与的复杂信号通路予以实现。
鉴于目前人们对PPAR—γ信号通路尚不甚清，PPARs 通常是通过与9-cis维甲酸受体( RXR)结合实现其转录活性的。
2 MAPK信号通路:mapk简介:丝裂原激活蛋白激酶（mitogen—activated protein kinase，MAPK）是广泛存在于动植物细胞中的一类丝氨酸/苏氨酸蛋白激酶。
作用主要是将细胞外刺激信号转导至细胞及其核内，并引起细胞的生物化学反应（增殖、分化、凋亡、应激等）。
：包括ERK1、MAPKs家族的亚族 :ERKs（extracellular signal regulated kinase)ERK2。
生长因子、细胞因子或激素激活此通路，介导细胞增殖、分化。
JNKs(c-Jun N-terminal kinase)包括JNK1、JNK2、JNK3。
细胞常见信号通路图片合集
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信号通路(2004-7-17)•·Erk和PI-3K在细胞外间质中的作用(2004-7-17)•·内质网相关的蛋白质降解通路示意图(2004-7-17)•·EPO售转导机制图(2004-7-17)•·血小板凝聚示意图(2004-7-17)•·NDK动力学(2004-7-17)•·线粒体的电子传递链示意图(2004-7-17)•·Eicosanoid代谢(2004-7-17)•·EGF信号通路(2004-7-17)•·calcineurin对Keratinocyte分化的影响(2004-7-17)•·E2F1信号通路(2004-7-17)•·MTA-3在雌激素不敏感性乳腺癌中下调(2004-7-17)•·双链RNA诱导基因表达示意图(2004-7-17)•·Dicer信号通路（RNAi机理）(2004-7-17)•·CDK5在老年性痴呆中的调节作用(2004-7-17)•·树突状细胞调节TH1和TH2发育示意图(2004-7-17)•·RAR和RXR被蛋白酶体降解通路(2004-7-17)•·D4-GDI信号通路示意图(2004-7-17)•·细胞因子和炎症反应示意图(2004-7-9)•·细胞因子网络调控图(2004-7-9)•·CFTR和beta 2肾上腺素受体通路(2004-7-9)•·Cyclin和细胞周期调控图(2004-7-9)•·Ran核质循环转运图(2004-7-9)•·Cyclin E降解通路图(2004-7-9)•·CXCR4信号通路图(2004-7-9)•·CTL介导的免疫反应图(2004-7-9)•·CTCF：第一个多价核因子(2004-7-9)•·皮质激素和心脏保护(2004-7-9)•·骨骼肌的成肌信号图(2004-7-9)•·VitD调控基因表达信号图(2004-7-9)•·补体信号通路(2004-7-9)•·线粒体和过氧化物酶体中β氧化的比较图(2004-7-9)•·经典的补体信号通路图(2004-7-9)•·心律失常的分子机制图(2004-7-9)•·hSWI/SNF ATP依赖的染色体重塑(2004-7-9)•·碳水化合物和cAMP调节ChREBP图(2004-7-9)•·分子伴侣调节干扰素信号图(2004-7-9)•·Ceramide信号图(2004-7-9)•·局部急性感染的细胞与分子信号(2004-7-9)•·细胞与细胞粘附信号(2004-7-9)•·细胞周期G2/M调控点信号调节(2004-7-9)•·细胞周期 G1/S调控点信号图(2004-7-9)•·CDK调节DNA复制(2004-7-9)•·cdc25和chk1在DNA破坏中的作用图(2004-7-9)•·CD40L信号通路图(2004-7-9)•·CCR3信号图(2004-7-9)•·CBL下调EGF受体的信号转导图(2004-7-9)•·一些氨基酸的代谢通路图 3 (2004-7-9)•·一些氨基酸的代谢通路图 2 (2004-7-9)•·一些氨基酸的代谢通路图(2004-7-9)•·Catabolic pathway for asparagine and asp (2004-7-9)•·Caspase 信号级联通路在细胞凋亡中的作用(2004-7-9)•·CARM1和雌激素的信号转导调控(2004-7-9)•·抗氧自由基的心脏保护作用信号转导图(2004-7-9)•·乙肝病毒中的钙信号调控(2004-7-9)•·镉诱导巨噬细胞的DNA合成和增殖(2004-7-9)•·Ca2+/CaM依赖的激活(2004-7-9)•·B细胞活化机理图(2004-6-9)•·BTG家族蛋白和细胞周期的调节(2004-6-9)•·BRCA1作用机理(2004-6-9)•·骨重塑示意图(2004-6-9)•·Botulinum Toxin阻断神经递质释放示意图(2004-6-9)•·缬氨酸的生物合成图(2004-6-9)•·Tryptophan在植物和细菌内的生物合成(2004-6-9)•·苏氨酸和蛋氨酸的体内合成示意图(2004-6-9)•·sphingolipids生物合成(2004-6-9)•·spermidine和spermine生物合成(2004-6-9)•·细菌体内合成脯氨酸的示意图(2004-6-9)•·苯丙氨酸和酪氨酸的生物合成(2004-6-9)•·神经递质的合成示意图(2004-6-9)•·赖氨酸生物合成图(2004-6-9)•·亮氨酸的体内生物合成图(2004-6-9)•·异亮氨酸的生物合成图(2004-6-9)•·甘氨酸和色氨酸的生物合成(2004-6-9)•·Cysteine在哺乳动物中的合成图(2004-6-9)•·Cysteine在细菌和植物内生物合成图(2004-6-9)•·Chorismate在细菌和植物内的生物合成(2004-6-9)•·Arginine在细菌内的生物合成(2004-6-9)•·生物活性肽诱导的通路(2004-6-9)•·脂肪酸的β氧化通路(2004-6-9)•·BCR信号通路示意图(2004-6-9)•·SUMOylation基本机理(2004-6-9)•·PPAR影响基因表达的基本信号机制图(2004-6-9)•·B淋巴细胞表面分子示意图(2004-6-9)•·B细胞生存信号通路(2004-6-5)•·B细胞信号通路的复杂性(2004-6-5)•·GPCR信号的衰减的机理(2004-6-4)•·ATM信号通路(2004-6-4)•·阿斯匹林的抗凝机理(2004-6-4)•·细胞凋亡信号调节DNA片段化(2004-6-4)•·细胞凋亡DNA片段化与组织稳态的机理(2004-6-4)•·反义核酸的作用机理---RNA polymerase III (2004-6-4)•·抗原递呈与处理信号图(2004-6-4)•·Antigen依赖的B细胞激活(2004-6-4)•·Anthrax Toxin Mechanism of Action (2004-6-4)•·血管紧张素转换酶2调节心脏功能(2004-6-4)•·Angiotensin II 介导JNK信号通路的激活(2004-6-4)•·Alternative Complement Pathway (2004-6-4)•·Alpha-synuclein和Parkin在怕金森病中的作用(2004-6-4)•·ALK在心肌细胞中的功能图(2004-6-4)•·AKT信号通路(2004-6-4)•·AKAP95在有丝分裂中的作用图(2004-6-4)•·Ahr信号转导图(2004-6-4)•·Agrin突触后的功能图(2004-6-4)•·ADP-Ribosylation 因子(2004-6-4)•·淋巴细胞粘附分子信号图(2004-6-4)•·Adhesion and Diapedesis of Lymphocytes (2004-6-4)•·Adhesion and Diapedesis of Granulocytes (2004-6-4)•·急性心肌梗死信号转导图(2004-6-4)•·src蛋白质激活图(2004-6-4)•·PKC与G蛋白耦联受体的关系(2004-6-4)•·cAMP依赖的CSK抑制T细胞功能示意图(2004-6-4)•·PKA功能示意图(2004-6-4)•·一氧化氮（NO）在心脏中的功能示意图(2004-6-4)•·RelA 在细胞核内乙酰化和去乙酰化(2004-6-4)actin肌丝Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works.Activation by Wave-1, another member of the WASP family, also induces actin alterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, theWiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function.Cory GO, Ridley AJ. Cell motility: braking WAVEs. Nature. 2002 Aug 15;418(6899):732-3. No abstract available.Eden, S., et al. (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899), 790-3Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood. 2002 Sep 15;100(6):2113-22.Kreishman-Deitrick M, Rosen MK, Kreishman-Deltrick M. Ignition of a cellular machine. Nat Cell Biol. 2002 Feb;4(2):E31-3. No abstract available.Machesky, L.M., Insall, R.H. (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8(25), 1347-56Robinson, R.C. et al. (2001) Crystal structure of Arp2/3 complex. Science 294(5547), 1679-84Weeds A, Yeoh S. Structure. Action at the Y-branch. Science. 2001 Nov 23;294(5547):1660-1. No abstract available.Wnt/LRP6 信号Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signalingWNT信号转导West Nile 西尼罗河病毒West Nile virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, Kunjin virus, yellow fever virus, Dengue virus, and Japanese encephalitis virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. WNV has rapidly spread across the United States through its insect host and causes neurological symptoms and encephalitis, which can result in paralysis or death. Since 1999 about 3700 cases of West Nile virus (WNV) infection and 200 deaths have been recorded in United States. The viral capsid protein likely contributes to the WNV-associated deadly inflammation via apoptosis induced through the mitochondrial pathway.WNV particles (50 nm in diameter) consist of a dense core (viral protein C encapsidated virus RNA genome)surrounded by a membrane envelope (viral E and M proteins embedded in a lipid bilayer). The virus binds to a specific cell surface protein (not yet identified), an interaction thought to involve E protein with highly sulfated neperan sulfate (HSHS) residues that are present on the surfaces of many cells and enters the cell by a process similar to that of endocytosis. Once inside the cell, the genome RNA is released into the cytoplasm via endosomal release, a fusion process involving acidic pH induced conformation change in the E protein. The RNA genome serves as mRNA and is translated by ribosomes into ten mature viral proteins are produced via proteolytic cleavage, which include three structural components and seven different nonstructural components of the virus. These proteins assemble and transcribe complimentary minus strand RNAs from the genomic RNA. The complimentary minus strand RNA in turns serves as template for the synthesis of positive-stranded genomic RNAs. Once viral E, preM and C proteins have accumulated to sufficient level, they assemble with the genomic RNA to form progeny virions, which migrate to the cell surface where they are surrounded with lipid envelop and released.Vitamin C 维生素C在大脑中的作用Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes thatpost-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import of dietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles. Svct2 imports reduced ascorbate from the plasma into veryactive tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1. Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.视觉信号转导信息来源：本站原创生物谷网站The signal transduction cascade responsible for sensing light in vertebrates is one of the best studied signal transduction processes, and is initiated by rhodopsin in rod cells, a member of the G-protein coupled receptor gene family. Rhodopsin remains the only GPCR whose structure has been resolved at high resolution. Rhodopsinin the discs of rod cells contains a bound 11-cis retinal chromophore, a small molecule derived from Vitamin A that acts as the light sensitive portion of the receptor molecule, absorbing light to initiate the signal transduction cascade. When light strikes 11-cis retinal and is absorbed, it isomerizes to all-trans retinal, changing the shape of the molecule and the receptor it is bound to. This change in rhodopsin抯shape alters its interaction with transducin, the member of the G-protein gene family that is specific in its role in visual signal transduction. Activation of transducin causes its alpha subunit to dissociate from the trimer and exchange bound GDP for GTP, activating in turn a membrane-bound cyclic-GMP specific phosphodiesterase that hydrolyzes cGMP. In the resting rod cell, high levels of cGMP associate with a cyclic-GMP gated sodium channel in the plasma membrane, keeping the channels open and the membrane of the resting rod cells depolarized. This is distinct from synaptic generation of action potentials, in which stimulation induces opening of sodium channels and depolarization. When cGMP gated channels in rod cells open, both sodium and calcium ions enter the cell, hyperpolarizing the membrane and initiating the electrochemical impulse responsible for conveying the signal from the sensory neuron to the CNS. The rod cell in the resting state releases high levels of the inhibitory neurotransmitter glutamate, while the release of glutamate is repressed by the hyperpolarization in the presence of light to trigger a downstream action potential by ganglion cells that convey signals to the brain. The calcium which enters the cell also activates GCAP, which activates guanylate cyclase (GC-1 and GC-2) to rapidly produce more cGMP, ending the hyperpolarization and returning the cell to its resting depolarized state. A protein called recoverin helps mediate the inactivation of the signal transduction cascade, returning rhodopsin to its preactivated state, along with the rhodopsin kinase Grk1. Phosphorylation of rhodopsin by Grkl causes arrestin to bind, helping to terminate the receptor activation signal. Dissociation and reassociation of retinal, dephosphorylation of rhodopsin and release of arrestin all return rhodopsin to its ready state, prepared once again to respond to light.VEGF，低氧信息来源：本站原创生物谷网站Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of the VEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA.. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubularsystem of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at a post-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.TSP-1诱导细胞凋亡信息来源：本站原创生物谷网站As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.Trka信号转导信息来源：本站原创生物谷网站Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkAthrough association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation.dbpb调节mRNA信息来源：本站原创生物谷网站Endothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation.RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway.CARM1甲基化信息来源：本站原创生物谷网站Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks。
细胞常见信号通路图片
目录actin肌丝...........................................................Wnt/LRP6?信号.......................................................WNT信号转导.........................................................West?Nile?西尼罗河病毒..............................................Vitamin?C?维生素C在大脑中的作用....................................视觉信号转导........................................................VEGF，低氧..........................................................TSP-1诱导细胞凋亡...................................................Trka信号转导........................................................dbpb调节mRNA .......................................................CARM1甲基化.........................................................CREB转录因子........................................................TPO信号通路.........................................................Toll-Like?受体......................................................TNFR2?信号通路......................................................TNFR1信号通路.......................................................IGF-1受体...........................................................TNF/Stress相关信号..................................................共刺激信号..........................................................Th1/Th2?细胞分化....................................................TGF?beta?信号转导...................................................端粒、端粒酶与衰老..................................................TACI和BCMA调节B细胞免疫...........................................T辅助细胞的表面受体.................................................T细胞受体信号通路...................................................T细胞受体和CD3复合物............................................... Cardiolipin的合成...................................................Synaptic突触连接中的蛋白............................................HSP在应激中的调节的作用.............................................Stat3?信号通路......................................................SREBP控制脂质合成...................................................酪氨酸激酶的调节....................................................Sonic?Hedgehog?(SHH)受体ptc1调节细胞周期...........................Sonic?Hedgehog?(Shh)?信号...........................................SODD/TNFR1信号......................................................AKT/mTOR在骨骼肌肥大中的作用........................................G蛋白信号转导.......................................................IL1受体信号转导.....................................................acetyl从线粒体到胞浆过程............................................趋化因子chemokine在T细胞极化中的选择性表达........................SARS冠状病毒蛋白酶..................................................SARS冠状病毒蛋白酶..................................................Parkin在泛素-蛋白酶体中的作用....................................... nicotinic?acetylcholine受体在凋亡中的作用........................... 线粒体在细胞凋亡中的作用............................................ MEF2D在T细胞凋亡中的作用........................................... Erk5和神经元生存.................................................... ERBB2信号转导....................................................... GPCRs调节EGF受体................................................... BRCA1调节肿瘤敏感性................................................. Rho细胞运动的信号................................................... Leptin能逆转胰岛素抵抗.............................................. 转录因子DREAM调节疼敏感............................................ PML调节转录......................................................... p27调节细胞周期..................................................... MAPK信号调节........................................................ 细胞因子调节造血细胞分化............................................ eIF4e和p70?S6激酶调节.............................................. eIF2调节............................................................ 谷氨酸受体调节ck1/cdk5 .............................................. BAD磷酸化调节....................................................... plk3在细胞周期中的作用.............................................. Reelin信号通路...................................................... RB肿瘤抑制和DNA破坏................................................ NK细胞介导的细胞毒作用.............................................. Ras信号通路......................................................... Rac?1细胞运动信号................................................... PTEN依赖的细胞生长抑制和细胞凋亡.................................... 蛋白激酶A（PKA）在中心粒中的作用.................................... notch信号通路....................................................... 蛋白酶体Proteasome复合物........................................... Prion朊病毒的信号通路............................................... 早老素Presenilin在notch和wnt信号中的作用......................... 淀粉样蛋白前体信号.................................................. mRNA的poly(A)形成.................................................. PKC抑制myosin磷酸化................................................ 磷脂酶C（PLC）信号.................................................. 巨噬细胞Pertussis?toxin不敏感的CCR5信号通路....................... Pelp1调节雌激素受体的活性........................................... PDGF信号通路........................................................ p53信号通路......................................................... p38MAPK信号通路..................................................... Nrf2是氧化应激基本表达的关键基因.................................... OX40信号通路........................................................ hTert转录因子的调节作用............................................. hTerc转录调节活性图................................................. AIF在细胞凋亡中的作用............................................... Omega氧化通路.......................................................核受体在脂质代谢和毒性中的作用...................................... NK细胞中NO2依赖的IL-12信号通路.................................... TOR信号通路......................................................... NO信号通路.......................................................... NF-kB信号转导通路................................................... NFAT与心肌肥厚的示意图.............................................. 神经营养素及其表面分子.............................................. 神经肽VIP和PACAP防止活化T细胞凋亡图.............................. 神经生长因子信号图.................................................. 细胞凋亡信号通路.................................................... MAPK级联通路........................................................ MAPK信号通路图...................................................... BCR信号通路......................................................... 蛋白质乙酰化示意图.................................................. wnt信号通路......................................................... 胰岛素受体信号通路.................................................. 细胞周期在G2/M期的调控机理图....................................... 细胞周期G1/S检查点调控机理图....................................... Jak-STAT关系总表.................................................... Jak/STAT?信号....................................................... TGFbeta信号......................................................... NFkappaB信号........................................................ p38?MAPK信号通路.................................................... SAPK/JNK?信号级联通路............................................... 从G蛋白偶联受体到MAPK .............................................. MAPK pathwayMAPK级联信号图.......................................... eIF-4E和p70?S6激酶调控蛋白质翻译................................... eif2蛋白质翻译...................................................... 蛋白质翻译示意图.................................................... 线粒体凋亡通路...................................................... 死亡受体信号通路.................................................... 凋亡抑制通路........................................................ 细胞凋亡综合示意图.................................................. Akt/Pkb信号通路..................................................... MAPK/ERK信号通路.................................................... 哺乳动物MAPK信号通路............................................... Pitx2多步调节基因转录............................................... IGF-1R导致BAD磷酸化的多个凋亡路径.................................. 多重耐药因子........................................................ mTOR信号通路........................................................ Msp/Ron受体信号通路................................................. 单核细胞和其表面分子................................................ 线粒体的肉毒碱转移酶（CPT）系统..................................... METS影响巨噬细胞的分化.............................................. Anandamide，内源性大麻醇的代谢...................................... 黑色素细胞（Melanocyte）发育和信号..................................DNA甲基化导致转录抑制的机理图....................................... 蛋白质的核输入信号图................................................ PPARa调节过氧化物酶体的增殖......................................... 对乙氨基酚（Acetaminophen）的活性和毒性机理......................... mCalpain在细胞运动中的作用.......................................... MAPK信号图.......................................................... MAPK抑制SMRT活化................................................... 苹果酸和天门冬酸间的转化............................................ 低密度脂蛋白（LDL）在动脉粥样硬化中的作用........................... LIS1基因在神经细胞的发育和迁移中的作用图............................ Pyk2与Mapk相连的信号通路........................................... galactose代谢通路................................................... Lectin诱导补体的通路................................................ Lck和Fyn在TCR活化中的作用......................................... 乳酸合成图.......................................................... Keratinocyte分化图.................................................. 离子通道在心血管内皮细胞中的作用.................................... 离子通道和佛波脂（Phorbal?Esters）信号.............................. 内源性Prothrombin激活通路.......................................... Ribosome内化通路.................................................... 整合素（Integrin）信号通路.......................................... 胰岛素（Insulin）信号通路........................................... Matrix?Metalloproteinases ........................................... 组氨酸去乙酰化抑制剂抑制Huntington病............................... Gleevec诱导细胞增殖................................................. Ras和Rho在细胞周期的G1/S转换中的作用.............................. DR3，4，5受体诱导细胞凋亡........................................... AKT调控Gsk3图...................................................... IL-7信号转导........................................................ IL22可溶性受体信号转导图............................................ IL-2活化T细胞图.................................................... IL12和Stat4依赖的TH1细胞发育信号通路.............................. IL-10信号通路....................................................... IL?6信号通路........................................................ IL?5信号通路........................................................actin肌丝Mammalian cell motility requires actin polymerization in the direction of movement to change membrane shape and extend cytoplasm into lamellipodia. The polymerization of actin to drive cell movement also involves branching of actin filaments into a network oriented with the growing ends of the fibers near the cell membrane. Manipulation of this process helps bacteria like Salmonella gain entry into cells they infect. Two of the proteins involved in the formation of Y branches and in cell motility are Arp2 and Arp3, both members of a large multiprotein complex containing several other polypeptides as well. The Arp2/3 complex is localized at the Y branch junction and induces actin polymerization. Activity of this complex is regulated by multiple different cell surface receptor signaling systems, activating WASP, and Arp2/3 in turn to cause changes in cell shape and cell motility. Wasp and its cousin Wave-1 interact with the Arp2/3 complex through the p21 component of the complex. The crystal structure of the Arp2/3 complex has revealed further insights into the nature of how the complex works.Activation by Wave-1, another member of the WASP family, also induces actin alterations in response to Rac1 signals upstream. Wave-1 is held in an inactive complex in the cytosol that is activated to allow Wave-1 to associate with Arp2/3. While WASP is activated by interaction with Cdc42, Wave-1, is activated by interaction with Rac1 and Nck. Wave-1 activation by Rac1 and Nck releases Wave-1 with Hspc300 to activate actin Y branching and polymerization by Arp2/3. Different members of this gene family may produce different actin cytoskeletal architectures. The immunological defects associated with mutation of the WASP gene, the Wiskott-Aldrich syndrome for which WASP was named, indicates the importance of this system for normal cellular function.Cory GO, Ridley AJ. Cell motility: braking WAVEs. Nature. 2002 Aug 15;418(6899):732-3. No abstract available.Eden, S., et al. (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418(6899), 790-3Falet H, Hoffmeister KM, Neujahr R, Hartwig JH. Normal Arp2/3 complex activation in platelets lacking WASp. Blood. 2002 Sep 15;100(6):2113-22.Kreishman-Deitrick M, Rosen MK, Kreishman-Deltrick M. Ignition of a cellular machine. Nat Cell Biol. 2002 Feb;4(2):E31-3. No abstract available.Machesky, L.M., Insall, R.H. (1998) Scar1 and the related Wiskott-Aldrich syndrome protein, WASP, regulate the actin cytoskeleton through the Arp2/3 complex. Curr Biol 8(25), 1347-56 Robinson, R.C. et al. (2001) Crystal structure of Arp2/3 complex. Science 294(5547), 1679-84Weeds A, Yeoh S. Structure. Action at the Y-branch. Science. 2001 Nov 23;294(5547):1660-1. No abstract available.Wnt/LRP6?信号Wnt glycoproteins play a role in diverse processes during embryonic patterning in metazoa through interaction with frizzled-type seven-transmembrane-domain receptors (Frz) to stabilize b-catenin. LDL-receptor-related protein 6 (LRP6), a Wnt co-receptor, is required for this interaction. Dikkopf (dkk) proteins are both positive and negative modulators of this signalingWNT信号转导West?Nile?西尼罗河病毒West Nile virus (WNV) is a member of the Flaviviridae, a plus-stranded virus family that includes St. Louis encephalitis virus, Kunjin virus, yellow fever virus, Dengue virus, and Japanese encephalitis virus. WNV was initially isolated in 1937 in the West Nile region of Uganda and has become prevalent in Africa, Asia, and Europe. WNV has rapidly spread across the United States through its insect host and causes neurological symptoms and encephalitis, which can result in paralysis or death. Since 1999 about 3700 cases of West Nile virus (WNV) infection and 200 deaths have been recorded in United States. The viral capsid protein likely contributes to theWNV-associated deadly inflammation via apoptosis induced through the mitochondrial pathway.WNV particles (50 nm in diameter) consist of a dense core (viral protein C encapsidated virus RNA genome) surrounded by a membrane envelope (viral E and M proteins embedded in a lipid bilayer). The virus binds to a specific cell surface protein (not yet identified), an interaction thought to involve E protein with highly sulfated neperan sulfate (HSHS) residues that are present on the surfaces of many cells and enters the cell by a process similar to that of endocytosis. Onceinside the cell, the genome RNA is released into the cytoplasm via endosomal release, a fusion process involving acidic pH induced conformation change in the E protein. The RNA genome serves as mRNA and is translated by ribosomes into ten mature viral proteins are produced via proteolytic cleavage, which include three structural components and seven different nonstructural components of the virus. These proteins assemble and transcribe complimentary minus strand RNAs from the genomic RNA. The complimentary minus strand RNA in turns serves as template for the synthesis of positive-stranded genomic RNAs. Once viral E, preM and C proteins have accumulated to sufficient level, they assemble with the genomic RNA to form progeny virions, which migrate to the cell surface where they are surrounded with lipid envelop and released.Vitamin?C?维生素C在大脑中的作用Vitamin C (ascorbic acid) was first identified by virtue of the essential role it plays in collagen modification, preventing the nutritional deficiency scurvy. Vitamin C acts as a cofactor for hydroxylase enzymes that post-translationally modify collagen to increase the strength and elasticity of tissues. Vitamin C reduces the metal ion prosthetic groups of many enzymes, maintaining activity of enzymes, also acts as an anti-oxidant. Although the prevention of scurvy through modification of collagen may be the most obvious role for vitamin C, it is not necessarily the only role of vitamin C. Svct1 and Svct2 are ascorbate transporters for vitamin C import into tissues and into cells. Both of these transporters specifically transport reduced L-ascorbic acid against a concentration gradient using the intracellular sodium gradient to drive ascorbate transport. Svct1 is expressed in epithelial cells in the intestine, upregulated in cellular models for intestinal epithelium and appears to be responsible for the import of dietary vitamin C from the intestinal lumen. The vitamin C imported from the intestine is present in plasma at approximately 50 uM, almost exclusively in the reduced form, and is transported to tissues to play a variety of roles.Svct2 imports reduced ascorbate from the plasma into very active tissues like the brain. Deletion in mice of the gene for Svct2 revealed that ascorbate is required for normal development of the lungs and brain during pregnancy. A high concentration of vitamin C in neurons of the developing brain may help protect the developing brain from free radical damage. The oxidized form of ascorbate, dehydroascorbic acid, is transported into a variety of cells by the glucose transporter Glut-1.Glut-1, Glut-3 and Glut-4 can transport dehydroascorbate, but may not transport significant quantities of ascorbic acid in vivo.视觉信号转导The signal transduction cascade responsible for sensing light in vertebrates is one of the best studied signal transduction processes, and is initiated by rhodopsin in rod cells, a member of the G-protein coupled receptor gene family. Rhodopsin remains the only GPCR whose structure has been resolved at high resolution. Rhodopsin in the discs of rod cells contains a bound 11-cis retinal chromophore, a small molecule derived from Vitamin A that acts as the light sensitive portion of the receptor molecule, absorbing light to initiate the signal transduction cascade. When light strikes 11-cis retinal and is absorbed, it isomerizes to all-trans retinal, changing the shape of the molecule and the receptor it is bound to. This change inrhodopsin抯 shape alters its interaction with transducin, the member of theG-protein gene family that is specific in its role in visual signal transduction. Activation of transducin causes its alpha subunit to dissociate from the trimer and exchange bound GDP for GTP, activating in turn a membrane-bound cyclic-GMP specific phosphodiesterase that hydrolyzes cGMP. In the resting rod cell, high levels of cGMP associate with a cyclic-GMP gated sodium channel in the plasma membrane, keeping the channels open and the membrane of the resting rod cells depolarized. This is distinct from synaptic generation of action potentials, in which stimulation induces opening of sodium channels and depolarization. When cGMP gated channels in rod cells open, both sodium and calcium ions enter the cell, hyperpolarizing the membrane and initiating the electrochemical impulse responsible for conveying the signal from the sensory neuron to the CNS. The rod cell in the resting state releases high levels of the inhibitory neurotransmitter glutamate, while the release of glutamate is repressed by the hyperpolarization in the presence of light to trigger a downstream action potential by ganglion cells that convey signals to the brain. The calcium which enters the cell also activates GCAP, which activates guanylate cyclase (GC-1 and GC-2) to rapidly produce more cGMP, ending the hyperpolarization and returning the cell to its resting depolarized state. A protein called recoverin helps mediate the inactivation of the signal transduction cascade, returning rhodopsin to its preactivated state, along with the rhodopsin kinase Grk1. Phosphorylation of rhodopsin by Grkl causes arrestin to bind, helping to terminate the receptor activation signal. Dissociation and reassociation of retinal, dephosphorylation of rhodopsin and release of arrestin all return rhodopsin to its ready state, prepared once again to respond to light.VEGF，低氧Vascular endothelial growth factor (VEGF) plays a key role in physiological blood vessel formation and pathological angiogenesis such as tumor growth and ischemic diseases. Hypoxia is a potent inducer of VEGF in vitro. The increase in secreted biologically active VEGF protein from cells exposed to hypoxia is partly because of an increased transcription rate, mediated by binding of hypoxia-inducible factor-1 (HIF1) to a hypoxia responsive element in the 5'-flanking region of theVEGF gene. bHLH-PAS transcription factor that interacts with the Ah receptor nuclear translocator (Arnt), and its predicted amino acid sequence exhibits significant similarity to the hypoxia-inducible factor 1alpha (HIF1a) product. HLF mRNA expression is closely correlated with that of VEGF mRNA.. The high expression level of HLF mRNA in the O2 delivery system of developing embryos and adult organs suggests that in a normoxic state, HLF regulates gene expression of VEGF, various glycolytic enzymes, and others driven by the HRE sequence, and may be involved in development of blood vessels and the tubular system of lung. VEGF expression is dramatically induced by hypoxia due in large part to an increase in the stability of its mRNA. HuR binds with high affinity and specificity to the VRS element that regulates VEGF mRNA stability by hypoxia. In addition, an internal ribosome entry site (IRES) ensures efficient translation of VEGF mRNA even under hypoxia. The VHL tumor suppressor (von Hippel-Lindau) regulates also VEGF expression at apost-transcriptional level. The secreted VEGF is a major angiogenic factor that regulates multiple endothelial cell functions, including mitogenesis. Cellular and circulating levels of VEGF are elevated in hematologic malignancies and are adversely associated with prognosis. Angiogenesis is a very complex, tightly regulated, multistep process, the targeting of which may well prove useful in the creation of novel therapeutic agents. Current approaches being investigated include the inhibition of angiogenesis stimulants (e.g., VEGF), or their receptors, blockade of endothelial cell activation, inhibition of matrix metalloproteinases, and inhibition of tumor vasculature. Preclinical, phase I, and phase II studies of both monoclonal antibodies to VEGF and blockers of the VEGF receptor tyrosine kinase pathway indicate that these agents are safe and offer potential clinical utility in patients with hematologic malignancies.TSP-1诱导细胞凋亡As tissues grow they require angiogenesis to occur if they are to be supplied with blood vessels and survive. Factors that inhibit angiogenesis might act as cancer therapeutics by blocking vessel formation in tumors and starving cancer cells. Thrombospondin-1 (TSP-1) is a protein that inhibits angiogenesis and slows tumor growth, apparently by inducing apoptosis of microvascular endothelial cells that line blood vessels. TSP-1 appears to produce this response by activating a signaling pathway that begins with its receptor CD36 at the cell surface of the microvascular endothelial cell. The non-receptor tyrosine kinase fyn is activated by TSP-1 through CD36, activating the apoptosis inducing proteases like caspase-3 and p38 protein kinases. p38 is a mitogen-activated kinase that also induces apoptosis in some conditions, perhaps through AP-1 activation and the activation of genes that lead to apoptosis.Trka信号转导Nerve growth factor (NGF) is a neurotrophic factor that stimulates neuronal survival and growth through TrkA, a member of the trk family of tyrosine kinase receptors that also includes TrkB and TrkC. Some NGF responses are also mediated or modified by p75LNTR, a low affinity neurotrophin receptor. Binding of NGF to TrkA stimulates neuronal survival, and also proliferation. Pathways coupled to these responses are linked to TrkA through association of signaling factors with specific amino acids in the TrkA cytoplasmic domain. Cell survival through inhibition of apoptosis is signaled through activation of PI3-kinase and AKT. Ras-mediated signaling and phospholipase C both activate the MAP kinase pathway to stimulate proliferation.dbpb调节mRNAEndothelial cells respond to treatment with the protease thrombin with increased secretion of the PDGF B-chain. This activation occurs at the transcriptional level and a thrombin response element was identified in the promoter of the PDGF B-chain gene. A transcription factor called the DNA-binding protein B (dbpB) mediates the activation of PDGF B-chain transcription in response to thrombin treatment. DbpB is a member of the Y box family of transcription factors and binds to both RNA and DNA. In the absence of thrombin, endothelial cells contain a 50 kD form of dbpB that binds RNA in the cytoplasm and may play a role as a chaperone for mRNA. The 50 kD version of dbpB also binds DNA to regulate genes containing Y box elements in their promoters. Thrombin activation results in the cleavage of dbpB to a 30 kD form. The proteolytic cleavage releases dbpB from RNA in the nucleus, allowing it to enter the nucleus and binds to a regulatory element distinct from the site recognized by the full length 50 kD dbpB. The genes activated by cleaved dbpB include the PDGF B chain. Dephosphorylation of dbpB also regulates nuclear entry and transcriptional activation.RNA digestion in vitro can release dbpB in its active form, suggesting that the protease responsible for dbpB may be closely associated in a complex. Identification of the protease that cleaves dbpB, the mechanisms of phosphorylation and dephosphorylation, and elucidation of the signaling path by which thrombin induces dbpB will provide greater understanding of this novel signaling pathway.CARM1甲基化Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms ofpost-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known.CREB转录因子The transcription factor CREB binds the cyclic AMP response element (CRE) and activates transcription in response to a variety of extracellular signals including neurotransmitters, hormones, membrane depolarization, and growth and neurotrophic factors. Protein kinase A and the calmodulin-dependent protein kinases CaMKII stimulate CREB phosphorylation at Ser133, a key regulatory site controlling transcriptional activity. Growth and neurotrophic factors also stimulate CREB phosphorylation at Ser133. Phosphorylation occurs at Ser133 via p44/42 MAP Kinase and p90RSK and also via p38 MAP Kinase and MSK1. CREB exhibit deficiencies in spatial learning tasks, while flies overexpressing or lacking CREB show enhanced or diminished learning, respectively.。
细胞信号通路大全
信号通路与免疫系统疾病
自身免疫疾病
自身免疫疾病患者体内免疫细胞信号通路异 常激活，如T细胞、B细胞等信号通路，导致 自身免疫反应过度。
炎症性疾病
炎症性疾病患者体内炎症细胞信号通路异常激活， 如NF-κB、MAPK等信号通路，导致炎症反应过度 或持续。
感染性疾病
感染性疾病患者体内病原微生物通过干扰免 疫细胞信号通路，如细菌、病毒等，逃避免 疫细胞的攻击。
PI3K-Akt信号通路
PI3K-Akt信号通路是细胞生存和增殖的关键信号转导途径。
PI3K-Akt信号通路在细胞生长、代谢、存活和凋亡等过程中发挥重要作用。当细胞受到生长因子、激素等刺激时，PI3K被激 活，进而催化生成PIP3，后者与Akt结合并使其磷酸化，从而激活Akt。Akt可以进一步调控下游的靶蛋白，参与细胞增殖、 迁移、代谢等过程。
JAK-STAT信号通路
JAK-STAT信号通路是细胞因子信号转导的重要途径之一。
JAK-STAT信号通路在细胞因子信号转导中发挥关键作用。当细胞因子与受体结合后，JAK被激活并催 化受体酪氨酸磷酸化，进而招募并磷酸化STAT蛋白。STAT蛋白形成二聚体并进入细胞核，调控靶基 因的表达，参与细胞生长、分化、免疫调节等过程。
信号通路的自调节
信号通路的正反馈调节
自调节的一种形式是正反馈调节，它通过增 加某个关键信号分子的数量或活性，进一步 增强自身的信号传递。例如，某些生长因子 可以诱导自身受体的表达，形成一个正反馈 环路，不断放大信号传递。
信号通路的负反馈调节
另一种自调节形式是负反馈调节，它通过降 低某个关键信号分子的数量或活性，来抑制 自身的信号传递。例如，某些激素可以通过 诱导产生拮抗性激素或受体，从而抑制自身 的信号传递。
细胞信号通路大全
细胞信号通路⼤全1 PPAR信号通路：过氧化物酶体增殖物激活受体( PPARs) 是与维甲酸、类固醇和甲状腺激素受体相关的配体激活转录因⼦超家族核激素受体成员。
它们作为脂肪传感器调节脂肪代谢酶的转录。
PPARs由PPARα、PPARβ和PPARγ 3种亚型组成。
PPARα主要在脂肪酸代谢⽔平⾼的组织，如：肝、棕⾊脂肪、⼼、肾和⾻骼肌表达。
他通过调控靶基因的表达⽽调节机体许多⽣理功能包括能量代谢、⽣长发育等。
另外，他还通过调节脂质代谢的⽣物感受器⽽调节细胞⽣长、分化与凋亡。
PPARa同时也是⼀种磷酸化蛋⽩，他受多种磷酸化酶的调节包括丝裂原激活蛋⽩激酶( ERK-和p38．M APK) ，蛋⽩激酶A和C( PKA，PKC) ，AM PK和糖原合成酶⼀3( G SK3) 等调控。
调控PPARa⽣长信号的酶报道有M APK、PKA和G SK3。
PPARβ⼴泛表达于各种组织，⽽PPAR γ主要局限表达在⾎和棕⾊脂肪，其他组织如⾻骼肌和⼼肌有少量表达。
PPAR-γ在诸如炎症、动脉粥样硬化、胰岛素抵抗和糖代谢调节，以及肿瘤和肥胖等⽅⾯均有着举⾜轻重的作⽤，⽽其众多⽣物学效应则是通过启动或参与的复杂信号通路予以实现。
鉴于⽬前⼈们对PPAR—γ信号通路尚不甚清，PPARs通常是通过与9-cis维甲酸受体( RXR)结合实现其转录活性的。
2 MAPK信号通路:mapk简介:丝裂原激活蛋⽩激酶（mitogen—activated protein kinase，MAPK）是⼴泛存在于动植物细胞中的⼀类丝氨酸/苏氨酸蛋⽩激酶。
作⽤主要是将细胞外刺激信号转导⾄细胞及其核内，并引起细胞的⽣物化学反应（增殖、分化、凋亡、应激等）。
MAPKs家族的亚族 :ERKs（extracellular signal regulated kinase)：包括ERK1、ERK2。
⽣长因⼦、细胞因⼦或激素激活此通路，介导细胞增殖、分化。
JNKs(c-Jun N-terminal kinase)包括JNK1、JNK2、JNK3。
一张图看懂胃癌的信号通路及对应靶向药
7）HEDGEHOG(HH)通路
8）WNT通路
9）NOTCH 通路
10）HIPPO通路
各信号通路及靶向药见下图，图中黄色框中即为各通路对应的靶向药，绿色为已应用于临床，红色为临床前或早期研发阶段。请大家点击图片查看大
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主要信号通路及基因异常类型
各信号通路靶向药临床试验结果总结
各信号通路及靶向药见下图图中黄色框中即为各通路对应的靶向药绿色为已应用于临床红色为临床前或早期研发阶段
一张图看懂胃癌的信号通路及对应靶向药
胃癌的信号通路主要有：
1）ERBB通路：ERBB1, ERBB2;
2）VEGF通路；
3）PI3K/AKT/MTOR通路
4）பைடு நூலகம்HOA通路
5）JAK/STAT通路
6）胃癌干细胞通路