干货 细胞信号通路图解之MAPK通路【值得珍藏】
信号通路9—MAPK Signaling
信号通路9—MAPK SignalingAPExBIO图▲ MAPK信号通路图丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK， MAP kinase）是一种对丝氨酸，苏氨酸和酪氨酸特异的蛋白激酶（即丝氨酸/苏氨酸特异性蛋白激酶）。
由于MAPK是培养细胞在受到生长因子等丝裂原刺激时被激活而被鉴定的，因而得名。
MAPKs参与引导细胞反应至各类刺激物，如有丝分裂原，渗透压，热休克和促炎细胞因子。
MAPKs调节多种细胞功能，包括增殖，基因表达，分化，有丝分裂，细胞存活和凋亡。
MAPKs仅在真核生物中发现。
MAPKs属于CMGC（CDK / MAPK / GSK3 / CLK）激酶组。
CDK相关程度最大。
MAPK链由3类蛋白激酶组成：上游激活蛋白→MAPK激酶激酶（MAPKKK）→MAPK激酶（MAPKK）→MAPK，通过依次磷酸化将上游信号传递至下游应答分子。
经典的MAPK通路激活开始于细胞膜，在这里，小GTP酶和各种蛋白激酶磷酸化并激活MAPKKK（MAP kinase kinase kinase，MAP3K或MKKK，MAPK激酶激酶）。
随后，MAPKKK直接磷酸化MAPKK（MAP kinase kinase，MAP2K 或MKK，MAPK激酶），MAPKK一旦被激活就会磷酸化并激活MAPK。
MAPK 的激活导致特异性MAPK激活蛋白激酶（MAPKAPK，MAPK-activated protein kinase）的磷酸化和活化，例如RSK，MSK或MNK家族成员和MK2/3/5。
MKKK的4个亚族已得到鉴定：A. Raf亚族。
研究的最为透彻，包括B-Raf、A-Raf、Raf1。
B. MEKK亚族。
由4种MEKK构成：MEKK1~MEKK4。
C. 第三个亚族：ASK1和Tpl2。
D. 第四个亚族与上述三个有较大不同，它包括MST（mammalian sterile 20-like）、SPRK、MUK（MAPK upstream kinase）、TAK1，以及相关程度最小的MOS （molony sarcoma oncoprotein）。
mapk 通路 巨噬细胞极化靶基因-概述说明以及解释
mapk 通路巨噬细胞极化靶基因-概述说明以及解释1.引言1.1 概述巨噬细胞是一类重要的免疫细胞，它在机体的免疫反应中起到至关重要的作用。
当机体遭受到外部的病原微生物入侵或者组织发生损伤时，巨噬细胞会被激活并参与炎症反应和免疫应答过程。
巨噬细胞的活化状态或者称为巨噬细胞极化状态是决定巨噬细胞生物学功能和效应的一个关键因素。
MAPK（Mitogen-Activated Protein Kinase）通路作为一条重要的信号转导通路，能够参与许多生物学过程的调节。
在巨噬细胞中，MAPK 通路的活化和调控对巨噬细胞极化以及其所参与的免疫反应至关重要。
巨噬细胞的极化状态可以分为经典型（M1型）和替代型（M2型）两种。
经典型巨噬细胞具有较强的细菌杀伤能力和炎症介导作用，而替代型巨噬细胞则主要参与组织修复和抗炎反应。
巨噬细胞极化状态的调节和维持涉及到众多的靶基因。
这些靶基因在不同类型的巨噬细胞中表达水平和功能有所差异，在巨噬细胞极化过程中发挥着重要的调控作用。
因此，对巨噬细胞极化靶基因的深入研究能够帮助我们更好地理解巨噬细胞功能的调控机制，并有望为免疫相关疾病的治疗提供新的策略和思路。
本文将重点介绍MAPK通路在巨噬细胞极化中的作用以及巨噬细胞极化靶基因的重要性。
通过对相关文献的综述和整理，希望能够全面系统地呈现出MAPK通路与巨噬细胞极化的关系，为进一步的研究提供理论依据和启示。
同时，也希望本文能够为深入理解巨噬细胞的功能和免疫调控机制提供有益的参考。
1.2文章结构【1.2 文章结构】本文分为引言、正文和结论三部分，结构如下：1. 引言该部分首先对文章的研究主题进行概述，简要介绍MAPK通路和巨噬细胞极化的背景和重要性。
接着，详细说明文章的目的，即探讨MAPK 通路在巨噬细胞极化中的作用以及巨噬细胞极化靶基因的重要性。
2. 正文正文部分分为两个子部分：MAPK通路的概念和作用，以及巨噬细胞极化的概念和机制。
线粒体未折叠蛋白反应-mapk信号通路
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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.。
干货细胞信号通路图解之细胞凋亡信号通路【珍藏版】
干货细胞信号通路图解之细胞凋亡信号通路【珍藏版】（1）通路综述：细胞凋亡是一种受调节的细胞自杀机制,通常表现为核浓缩、起皱、膜发泡以及DNA片段化。
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。
XIAP抑制Caspase-3,-7,-9。
线粒体释放多种促凋亡因子,如Smac/Diablo、AIF、HtrA2、EndoG，和细胞色素C。
Smac/Diablo与XIAP结合，解除XIAP对凋亡的抑制。
Caspase-11被病理的促发炎信号和促凋亡信号诱导表达并激活，它能促进Caspase-1的活化,Caspase-1直接作用于caspase-3以促进凋亡和炎症反应。
Caspase-12和-7在内质网应激的情况下被激活。
抗凋亡生长因子和细胞因子激活 Akt和 p90RSK。
Akt 直接磷酸化并抑制Bad蛋白和间接抑制Bim的表达，这是通过磷酸化并抑制Bim所需的转录因子Fox0实现的。
Fox0通过上调促凋亡因子如FasL和Bim促进调亡。
（2）细胞生存需要积极的抑制凋亡发生，一方面需要抑制促凋亡因子的表达，另一方面则需要表达一些抗凋亡因子。
PI3K 通路被许多生存因子活化，能够激活Akt，Akt是生存信号传导中一个重要的角色。
PTEN抑制PI3K通路。
活化的Akt抑制促凋亡Bcl-2家族成员Bad，Bax，caspase-9，GSK-3和Fox01。
MAPK信号通路
MAPK信号通路2008-06-04 21:50MAPK,丝裂原活化蛋白激酶（mitogen-activated protein kinases，MAPKs）是细胞内的一类丝氨酸／苏氨酸蛋白激酶。
研究证实，MAPKs信号转导通路存在于大多数细胞内，在将细胞外刺激信号转导至细胞及其核内，并引起细胞生物学反应（如细胞增殖、分化、转化及凋亡等）的过程中具有至关重要的作用。
研究表明，MAPKs信号转导通路在细胞内具有生物进化的高度保守性，在低等原核细胞和高等哺乳类细胞内，目前均已发现存在着多条并行的MAPKs信号通路，不同的细胞外刺激可使用不同的MAPKs信号通路，通过其相互调控而介导不同的细胞生物学反应。
1并行MAPKs信号通路的组成及其活化特点在哺乳类细胞目前已发现存在着下述三条并行的MAPKs信号通路［1］。
1．1ERK（extracellular signal-regulated kinase）信号通路1986年由Sturgill等人首先报告的MAPK。
最初其名称十分混乱，曾根据底物蛋白称之为MAP2K、ERK、MBPK、RSKK、ERTK等。
此后，由于发现其具有共同的结构和生化特征，而被命名为MAPK。
近年来，随着不同MAPK家族成员的发现，又重新改称为ERK。
在哺乳类动物细胞中，与ERK相关的细胞内信号转导途径被认为是经典MAPK信号转导途径，目前对其激活过程及生物学意义已有了较深入的认识。
研究证实，受体酪氨酸激酶、G蛋白偶联的受体和部分细胞因子受体均可激活ERK信号转导途径。
如：生长因子与细胞膜上的特异受体结合，可使受体形成二聚体，二聚化的受体使其自身酪氨酸激酶被激活；受体上磷酸化的酪氨酸又与位于胞膜上的生长因子受体结合蛋白2（Grb2）的SH2结构域相结合，而Grb2的SH3结构域则同时与鸟苷酸交换因子SOS（Son of Sevenless）结合，后者使小分子鸟苷酸结合蛋白Ras的GDP解离而结合GTP，从而激活Ras；激活的Ras进一步与丝／苏氨酸蛋白激酶Raf-1的氨基端结合，通过未知机制激活Raf-1；Raf-1可磷酸化MEK1／MEK2（MAP kinase／ERK kinase）上的二个调节性丝氨酸，从而激活MEKs；MEKs为双特异性激酶，可以使丝／苏氨酸和酪氨酸发生磷酸化，最终高度选择性地激活ERK1和ERK2（即p44MAPK和p42MAPK）。
哺乳动物的三条mapk信号通路途经概述
p38 MAPK是1993年由Brewster等人在研究高渗环境对真菌的影响时发现的。以后又发现它也存在于哺乳动物的细胞内，也是MAPKs的亚类之一，其性质与JNK相似，同属应激激活的蛋白激酶。目前已发现p38MAPK有5个异构体，分别为p38α（p38）、p38β1、p38β2、p38γ、p38δ。其分布具有组织特异性：p38α、p38β1、p38β2在各种组织细胞中广泛存在，p38γ仅在骨骼肌细胞中存在，而p38δ主要存在于腺体组织。
有时，MAPKs的灭活并不依赖于双特异性磷酸酶。在PC12细胞，蛋白磷酸酶2A（PP2A）是ERK灭活的限速酶，同时可下调MEK的活性。由于PP2A主要位于胞浆中，因此，它主要灭活胞浆中的MAPKs。
MAPKs的灭活随其在细胞中的位置不同，由不同的磷酸酶灭活。PP2A、Pst-1、Pst-2可迅速灭活胞浆中的MAPKs，持续的MAPKs的激活，常伴有MAPKs转位到核，此时核中的MAPKs由位于细胞核中的双特异性磷酸酶MKP-1、PAC-1等灭活。此外，不同的MAPKs为不同的双特异性磷酸酶选择性灭活。
JNK／SAPK信号通路可被应激刺激（如紫外线、热休克、高渗刺激及蛋白合成抑制剂等）、细胞因子（TNFα，IL-1）、生长因子（EGF）及某些G蛋白偶联的受体激活。外界刺激可通过Ras依赖或非Ras依赖的两条途径激活JNK，小分子G蛋白Ras超家族的成员之一Rho可能也是JNK激活的上游信号，Rho蛋白Rac及cdc42的作用可能是与p21激活的丝／苏氨酸激酶PAK结合，使其自身磷酸化而被激活，而活化的PAK进一步使JNK激活。
在真菌中，并行的MAPKs信号通路在细胞信号转导中并无相互作用，其每一条MAPKs通路都是相对独立的，通常不与其它通路发生交联。能够维持这种相对独立的机制是由于存在着支架蛋白（如STE5），它可将外界信号激活的细胞信号通路中的各个信号分子结合到一起，形成复合物，起到生理性隔室化的效应，从而防止这条通路与其它通路发生交联。对真菌说来，不同的MAPKs通路调节不同的生理过程；对于同样的刺激，几条并行的通路并不同时被激活；其中一条通路若出现突变，也不影响其它通路的信号传递。
MAPK信号通路
MAPK 信号通路2008-06-04 21:50 MAPK, 丝裂原活化蛋白激酶( mitogen-activatedprotein kinases，MAPKs )是细胞内的一类丝氨酸／苏氨酸蛋白激酶。
研究证实，MAPKs 信号转导通路存在于大多数细胞内，在将细胞外刺激信号转导至细胞及其核内，并引起细胞生物学反应(如细胞增殖、分化、转化及凋亡等)的过程中具有至关重要的作用。
研究表明，MAPKs 信号转导通路在细胞内具有生物进化的高度保守性，在低等原核细胞和高等哺乳类细胞内，目前均已发现存在着多条并行的MAPKs 信号通路，不同的细胞外刺激可使用不同的MAPKs 信号通路，通过其相互调控而介导不同的细胞生物学反应。
1 并行MAPKs 信号通路的组成及其活化特点在哺乳类细胞目前已发现存在着下述三条并行的MAPKs 信号通路 [1]。
1．1 ERK (extracellular signal-regulated kinase)信号通路1986 年由Sturgill 等人首先报告的MAPK 。
最初其名称十分混乱，曾根据底物蛋白称之为MAP2K 、ERK、MBPK 、RSKK 、ERTK 等。
此后，由于发现其具有共同的结构和生化特征，而被命名为MAPK 。
近年来，随着不同MAPK 家族成员的发现，又重新改称为ERK 。
在哺乳类动物细胞中，与ERK 相关的细胞内信号转导途径被认为是经典MAPK 信号转导途径，目前对其激活过程及生物学意义已有了较深入的认识。
研究证实，受体酪氨酸激酶、G 蛋白偶联的受体和部分细胞因子受体均可激活ERK 信号转导途径。
如：生长因子与细胞膜上的特异受体结合，可使受体形成二聚体，二聚化的受体使其自身酪氨酸激酶被激活；受体上磷酸化的酪氨酸又与位于胞膜上的生长因子受体结合蛋白2( Grb2)的SH2 结构域相结合，而Grb2 的SH3 结构域则同时与鸟苷酸交换因子SOS( Son of Sevenless)结合，后者使小分子鸟苷酸结合蛋白Ras的GDP 解离而结合GTP，从而激活Ras；激活的Ras进一步与丝／苏氨酸蛋白激酶Raf-1 的氨基端结合，通过未知机制激活Raf-1；Raf-1 可磷酸化MEK1 ／MEK2 (MAP kinase／ERK kinase)上的二个调节性丝氨酸，从而激活MEKs ；MEKs 为双特异性激酶，可以使丝／苏氨酸和酪氨酸发生磷酸化，最终高度选择性地激活ERK1和ERK2(即p44MAPK 和p42MAPK )。
干货细胞信号通路图解之PI3KAkt信号通路
⼲货细胞信号通路图解之PI3KAkt信号通路丝/苏氨酸激酶Akt/PKB最初发现是作为⼀种原癌基因，现在已受到⼴泛的关注，因为其在很多的细胞活动中都起到关键性的作⽤，包括癌症的发展和胰岛素代谢。
Akt级联反应可以被许多机制激活，诸如受体酪氨酸激酶，整合素，B细胞和T细胞受体，细胞因⼦受体，G 蛋⽩偶联受体以及其他各种刺激，这些途径可以促使肌醇磷脂-3-激酶(PI3K )产⽣磷脂酰肌醇3，4，5 -三磷酸。
这些脂类物质为含有PH结构域(pleckstrin-homologydomain)的蛋⽩提供锚定位点，这些分⼦包括Akt和它的上游活化因⼦PDK1。
肿瘤抑制基因PTEN是⼀种公认的Akt的主要抑制剂，通常在⼈类肿瘤中会消失。
最近，越来越多的关注集中在磷酸酶（包括PHLIP）上，它能使Akt失活。
三种Akt的异构体(Akt1, Akt2,Akt3 )介导了许多 PI3K 调控的下游通路。
Akt是胰岛素信号传递和葡萄糖代谢中主要的调节分⼦，⼩⿏的遗传学研究发现Akt2 在这些过程中起关键作⽤。
另外，现在已经发现癌症和胰岛素代谢在病理情况下会出现Akt的种系突变。
Akt作⽤于TSC1/TSC2复合物和mTOR信号通路来调控细胞⽣长；作⽤于CDK 的抑制分⼦P21和P27，并间接影响cyclinD1和p53的表达⽔平来调控细胞周期和细胞增殖。
Akt可以通过直接抑制促凋亡信号如促凋亡调节者Bad和Forkhead家族转录因⼦来促进细胞的存活。
T淋巴细胞转运到淋巴组织这个过程是由Akt下游的粘附因⼦的表达来控制的。
Akt还能调控神经元功能相关蛋⽩如GABA受体,ataxin-1 和huntingtin 分⼦。
最近，Akt⼜被发现能和Smad 分⼦结合调节TGF β信号传导。
最后，Akt对核纤层蛋⽩A抗原的磷酸化在核蛋⽩的结构组织中发挥作⽤。
这些发现使Akt/PKB成为在治疗癌症，糖尿病，中风和神经退⾏性疾病中的重要靶点。
MAPK ERK信号通路图及简介
MAPK/ERK信号通路图及简介日期：2013-01-23 来源：互联网标签：信号通路MAPK相关专题：MAPK信号通路专题摘要: MAPK,丝裂原活化蛋白激酶(mitogen-activated protein kinases，MAPKs)是细胞内的一类丝氨酸/苏氨酸蛋白激酶。
研究证实，MAPKs信号转导通路存在于大多数细胞内，在将细胞外刺激信号转导至细胞及其核内，并引起细胞生物学反应(如细胞增殖、分化、转化及凋亡等)的过程中具有至关重要的作用。
研究表明，MAPKs 信号转导通路在细胞内具有生物进化的高度保守性，在低等原核细胞和高等哺乳类天隆科技NP968自动核酸提取仪，产品试用进行中！佛山泰尔健生物细胞培养器材诚征代理MAPK,丝裂原活化蛋白激酶(mitogen-activated protein kinases，MAPKs)是细胞内的一类丝氨酸/苏氨酸蛋白激酶。
研究证实，MAPKs信号转导通路存在于大多数细胞内，在将细胞外刺激信号转导至细胞及其核内，并引起细胞生物学反应(如细胞增殖、分化、转化及凋亡等)的过程中具有至关重要的作用。
研究表明，MAPKs 信号转导通路在细胞内具有生物进化的高度保守性，在低等原核细胞和高等哺乳类细胞内，目前均已发现存在着多条并行的MAPKs信号通路，不同的细胞外刺激可使用不同的MAPKs信号通路，通过其相互调控而介导不同的细胞生物学反应。
ERK(extracellular signal-regulated kinase)信号通路1986年由Sturgill等人首先报告的MAPK。
最初其名称十分混乱，曾根据底物蛋白称之为MAP2K、ERK、MBPK、RSKK、ERTK等。
此后，由于发现其具有共同的结构和生化特征，而被命名为MAPK。
近年来，随着不同MAPK家族成员的发现，又重新改称为ERK。
哺乳类动物细胞中，与ERK相关的细胞内信号转导途径被认为是经典MAPK 信号转导途径，目前对其激活过程及生物学意义已有了较深入的认识。
MAPK信号图
MAPK
丝裂原活化蛋白激酶（MAPK）途径是介导细胞反应的重要信号系统,普遍存在于多种生物中（包括酵母和哺乳动物细胞）,参与了细胞生长、发育、分裂、死亡以及细胞间的功能同步等多种生理反应的过程。
MAPK是一类丝氨酸/苏氨酸激酶,由多种同工酶组成。
自从1991年Sturgill及其同事在哺乳动物细胞鉴定出细胞外信号调节激酶（ERK）后[4],MAPK 信号通路的研究取得了迅猛发展。
除ERK外,还发现和克隆了C一JUN氨基末端激酶(JNK)/应激激活蛋白激酶（SAPK）、p38和ERK5/BMK1等MAPK亚族。
MAPK包括:
①细胞外信号调节的蛋白激酶（ERK）；
②C-Jun N端激酶（JUK）/应激激活的蛋白激酶(SAPK)；
③p38MAPK。
MAPK家族酶的激活机制相似,都通过磷酸化的三维酶促联反应
(MAP2KKK→MAPKK→MAPK)。
其中ERK通路主要被分裂原激活,如生长因子与受体结合后,能激活小G蛋白Ras,进而激活Raf→MEK→ERK通路;而JNK/SAPK通路能被多种应激源、促炎细胞因子和炎症反应介质等激活。
MAPK信号通路参与了细胞生长、发育、分裂和细胞间的功能同步等多种生理过程,并在细胞发生恶性转化等病理过程中起重要作用。
细胞信号通路
细胞信号通路细胞信号通路是指细胞内外环境改变时，细胞内部如何接收、转导和响应这些信号的一系列生化反应和调节机制。
细胞信号通路在维持细胞生命活动、发育和繁殖过程中起着至关重要的作用。
对于人类健康和疾病的研究，细胞信号通路也具有重要的理论和实践意义。
简介细胞信号通路是由一系列分子相互作用和信号传递构成的复杂网络。
这些分子包括受体、信号分子、信号转导蛋白和效应蛋白等。
细胞信号通路的重要组成部分为受体与配体相互作用，激活信号分子，最终调控细胞生物学效应。
信号通路类型细胞信号通路可以分为内源性和外源性信号通路。
内源性信号通路是指细胞通过与邻近细胞进行直接或间接的相互作用来传递信号。
而外源性信号通路是指细胞通过与外界分子或细胞进行相互作用来传递信号。
细胞信号通路的传递方式有多种，其中常见的包括激酶信号通路、G蛋白偶联受体信号通路和核内受体信号通路等。
这些信号通路可以独立工作，也可以相互配合，形成复杂的信号调控网络。
酶信号通路酶信号通路是细胞内最常见的信号传导机制之一。
主要通过激酶-底物反应来完成信号传递。
当外界信号分子与受体结合后，受体会激活下游酶，进而磷酸化下游底物分子。
磷酸化可以改变底物分子的结构和功能，从而调控细胞的生物学效应。
酶信号通路的代表性例子包括了丝裂原活化激酶（MAPK）信号通路。
这个信号通路在调控细胞的分裂、增殖和生长等生物学过程中起着重要作用。
MAPK信号通路可以通过多个中间分子的级联反应来传递信号，形成一个复杂的调控网络。
G蛋白偶联受体信号通路G蛋白偶联受体（GPCR）信号通路是另外一种常见的信号传导机制。
GPCR是一类在细胞膜上表达的受体，通过与G蛋白相互作用来传递信号。
当外界信号分子结合到GPCR上时，GPCR会与G蛋白结合，并激活G蛋白。
激活的G蛋白能够改变细胞内二信使的水平，如环磷酸腺苷（cAMP）和胞内钙离子等。
这些二信使能够进一步调控多种酶的活性和细胞内各种功能。
核内受体信号通路核内受体信号通路是一种与核内受体相互作用的信号传导机制。
mapk signaling pathway的表型-概述说明以及解释
mapk signaling pathway的表型-概述说明以及解释1.引言1.1 概述Mapk (Mitogen-activated protein kinase)信号通路是一种重要的细胞信号传导途径，能够调节细胞的生长、分化、存活以及细胞的代谢等过程。
通过一系列的激酶级联反应，Mapk信号通路可以将外部的刺激转化为细胞内的生物学响应。
这种信号通路在许多生命过程中发挥着关键作用，例如发育、组织再生、免疫应答以及细胞的应激反应等。
在Mapk信号通路中，MAPK激酶被磷酸化激活，并通过磷酸化下游靶点分子来传递信号。
其中包括ERK (Extracellular signal-regulated kinase)、JNK (c-Jun NH2-terminal kinase)以及p38 MAPK等重要的成员。
这些成员可以被细胞表面的受体激活，以及其他的内部信号分子的激活。
Mapk信号通路在细胞发育和生理过程中发挥着重要的调控作用。
它参与细胞增殖、分化和凋亡的调节，对于组织发育以及器官形成具有重要作用。
此外，Mapk信号通路还参与细胞代谢、细胞周期调控以及基因表达等多个生物学过程。
除了在正常生理过程中的重要作用外，Mapk信号通路在疾病中也扮演着重要角色。
它在多种疾病的发生和发展过程中起到关键性的调控作用。
例如，某些突变体或过度激活的Mapk信号通路成员可能导致细胞的恶性转化、肿瘤形成以及侵袭转移等。
此外，Mapk信号通路还与中风、炎症和神经退行性疾病等疾病的发生密切相关。
总而言之，Mapk信号通路在生命过程中扮演着重要角色。
它参与调节细胞的生长、分化和存活，并在疾病的发生和发展中发挥关键作用。
对于深入了解Mapk信号通路的功能及其在疾病中的作用机制，可以为疾病的治疗和预防提供重要的理论基础。
未来的研究将重点关注Mapk信号通路的调控网络、相互作用以及其潜在的药物靶点，以期为疾病治疗的开发提供新的途径。
文章结构部分主要介绍整篇文章的组织结构和各个章节的主要内容。
《MAPK信号通路》课件
MAPK信号通路与PI3K、JAK-STAT等其他信号通路相互作用，共同调节细胞的生长。
MAPK信号通路在细胞发育中的作用
MAPK信号通路对细胞分化的调控
01
MAPK信号通路通过调节特定基因的表达，促进细胞
的分化。
MAPK信号通路的级联反应与细胞发育
02 MAPK信号通路的级联反应能够传递并放大外部刺激
在疾病治疗中的应用前景
精准医疗
通过检测MAPK信号通路相关基因的突变或表达水平，可以为患者提供个性化的精准治 疗方案。
靶向治疗
针对MAPK信号通路中的关键蛋白，可以开发出具有靶向性的药物，提高治疗效果并降 低副作用。
在未来研究中的展望和挑战
01
深入探索MAPK信号 通路的调控机制
随着研究的深入，有望发现更多与 MAPK信号通路相互作用的蛋白和调 控因子，进一步揭示其调控机制。
PART 05
MAPK信号通路的调控机 制
REPORTING
酶促降解的调控
酶促降解是MAPK信号通路中重要的调控方式之一，通过降解MAPK的磷 酸化形式，可以终止信号的传递。
酶促降解主要通过蛋白酶体和溶酶体等途径实现，其中蛋白酶体主要降解 全长的蛋白质，而溶酶体则主要降解蛋白质的磷酸化形式。
酶促降解的调控对于维持细胞内稳态具有重要意义，可以防止信号过度传 递对细胞造成损害。
2023
REPORTING
PART 03
MAPK信号通路在细胞生 长、发育和分化中的作用
MAPK信号通路在细胞生长中的作用
MAPK信号通路对细胞生长的调控
MAPK信号通路通过调节细胞周期、细胞分裂和细胞大小，控制细胞的生长。
干货细胞信号通路图解之细胞代谢相关通路
干货细胞信号通路图解之细胞代谢相关通路（1）Insulin Receptor Signaling：胰岛素是控制关键的能量代谢功能如葡糖和脂代谢过程中的主要激素。
胰岛素激活胰岛素受体酪氨酸激酶，后者磷酸化并召集不同的底物接头蛋白如IRS家族蛋白。
IRS上酪氨酸被磷酸化后成为众多信号传导关联蛋白的结合位点。
其中，PI3K在胰岛素功能中起主要的作用，大部分是通过活化Akt/PKB和PKCζ级联来完成的。
活化的Akt通过抑制GSK-3诱导糖原的合成，通过mTOR和下游元件影响蛋白合成，通过抑制几个促凋亡分子(Bad，Forkhead家族转录因子，GSK-3)影响细胞生存。
胰岛素促进肌肉和脂肪细胞对葡糖的吸收，这是因为它能促使还有GLUT4的囊泡转移到细胞膜上。
GLUT4的移位需要PI3K/Akt通路的参与和IR介导的CAP 的磷酸化和形成CAP:Cbl:CrkII复合体。
胰岛素信号通路也会影响细胞生长和有丝分裂，主要是通过Akt级联进行，也会有Ras/MAPK通路的参与。
另外，胰岛素信号通路可以通过中断CREB/CBP/Torc2的结合抑制肝脏中的糖异生。
胰岛素信号通路还可以通过激活SREBP-1C，USF1和LXR来促进脂肪酸的合成。
从Akt/PKB，PKCζ，p70 S6K和MAPK级联得到的负反馈信息会导致丝氨酸的磷酸化和IRS信号通路的失活。
（2）AMPK Signaling：AMP激活的蛋白激酶( AMPK, AMP-activated protein kinase)是细胞能量稳态平衡调节的关键分子。
这个激酶的激活响应细胞耗竭胞内ATP的压力,如低葡萄糖,缺氧,缺血和热激。
该激酶是一个异质三聚体,由一个α催化亚基和β、γ调节亚基组成。
AMP与γ亚基结合后,该复合体发生异构化并激活,成为上游主要激酶AMPKK,LKB1更适合的底物，在α亚基的Thr172位发生磷酸化。
当代谢激素包括adiponectin和leptin刺激时，AMPK响应细胞内钙的改变也能被CAMKK2在Thr172直接磷酸化。
细胞常见信号通路图片合集
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)。
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干货细胞信号通路图解之MAPK通路【值得珍藏】
科研小助手原创，转载请注明来源。
公众号内回复“Cell Signaling Pathway”获取全套信号通路图本文由百度贴吧nosce吧吧主黄杰投稿一、MAPK信号通路：
（1）有丝分裂原激活的蛋白激酶(MAPK)是一族在真核生物中非常保守的丝/苏氨酸蛋白激酶，在许多细胞活动中起作用，如生长增殖，细胞分化，细胞运动或死亡。
MAPK级联信号传导由3 个不同层次的分子所组成。
MAPK被MAPK
的激酶( MAPKK)磷酸化后激活，MAPKK被MAPKK的激酶(MAPKKK )磷酸化而激活。
而MAPKKK通过与小GTPase和/或其他蛋白酶相互作用而被激活，从而将MAPK和细胞表面的受体以及胞外的信号联系在一起。
（2）许多参与生长和分化的受体都能够激活MAPK/ERK信号通路，比如说受体酪氨酸激酶(RTK)，整合素，和离子通道。
响应特定信号所涉及到的具体分子会相差很大，但通
路的结构是一致的，那就是接头分子(adaptor，如Shc, GRB2, Crk等)将鸟苷酸交换因子(SOS, C3G 等)和受体连接
在一起，然后把信号向小GTP 结合蛋白(Ras, Rap1)传递，后者又激活核心的级联反应，这是由一个MAPKKK( Raf) ，一个MAPKK( MEK1/2)和MAPK( Erk)所构成的。
活化的ERK 二聚体能调节胞浆中的目标分子，也可以转移到细胞核
中，然后对一系列转录因子进行磷酸化以调节基因表达。
SciRes（3）很多外部的刺激都能够激活G蛋白偶联受体(GPCR)。
在受体活化以后，G 蛋白将GDP 转换成GTP ，然后结合了GTP的α和β/γ亚基从受体脱离开，启动信号向胞内的传导。
与不同亚型的异质三聚体G 蛋白结合的受体可以采取不同的手段激活小G 蛋白/MAPK级联反应，至少有三个不同家族的酪氨酸激酶参与其中。
Src家族激酶响应活化的PI3Kγ，而后者被β/γ亚基激活。
它们还能够响应受体的内化，受体酪氨酸激酶的交叉活化，以及有Pyk2 和/或FAK参与的整合素途径信号。
GPCRs同样可以通过
PLCβ去激活PKC 和CaMKII ，对下游的MAPK通路可以有激活或抑制的影响。
SciRes（4）压力激活的蛋白激酶(Stress-activated protein kinase, SAPK)或称Jun氨基端激酶(Jun amino-terminal kinase, JNK) 是MAPK的家族成员，能被一系列的环境压力，炎症细胞因子，生长因子和GPCR激动剂所激活。
压力信号通过Rho家族的小GTP 酶(small GTPase)向这条级联通路传导，这些小GTP酶包括(Rac, Rho, cdc42) 。
和其他的MAPK情况一样，靠近膜的激酶是一个MAPKKK，一般是MEKK1-4 ，或者是一个混合激酶去磷酸化并激活MKK4(SEK)或MKK7，它们是SAPK/JNK的激酶。
另外，MKK4/7也可以被生发中心激酶(germinal center kinase, GCK)以一种GTPase 依赖的方式激活。
活化后的
SAPK/JNK转移到细胞核内调节多种转录因子。
（5）p38 MAPK(α,β,γ和δ)是MAPK的家族成员，它们被一些环境压力和炎症细胞因子激活。
和其他的MAPK级联结构一样，靠近细胞膜的成分是一个MAPKKK，一般是一个MEKK或者是一个混合激酶MLK (Mixed lineage kinase )。
这个MAPKKK磷酸化并激活MKK3/6，这是p38MAPK 的激酶。
当细胞受到凋亡刺激时，MKK3/6还可以被ASK1 激活。
p38MAPK 调节的下游分子包括HSP27，MK2(MAPKAPK-2)，MK3(MAPKAPK-3)和一些转录因子包括ATF-2，Stat-1，Max/Myc复合体，MEF-2，Elk-1 ，它还可以通过活化MSK1间接调节CREB分子。