ERK信号通路的信号转导调控机制

第29卷第1期2009年2月

国际病理科学与临床杂志 htt p://www .gjbl .net

I nternati onal Journal of Pathol ogy and ClinicalMedicine

Vol .29　No .1

Feb .　2009

收稿日期:2008-11-05 修回日期:2008-12-22

作者简介:赵明哲,硕士研究生,主要从事磷酸化蛋白质组学和质谱技术的研究。通讯作者:姜勇,E 2mail:yjiang@fi m mu .com

基金项目:国家自然科学基金(30670828,30670829,30572151);国家自然科学基金委员会-广东省人民政府自然科学联合基金

(U0632004)。　Thiswork was supported byNati onalNatural Science Foundati on (30670828,30670829,30572151)and Joint Fund of NSFC with the Guangdong Pr ovincial Government (U0632004).

ERK 信号通路的信号转导调控机制

赵明哲1,2,刘靖华2,李玉花1,姜勇2

(1.东北林业大学生命科学学院发育生物学实验室,哈尔滨150040;2.南方医科大学广东省蛋白质组学重点实验室,广州510515)

[摘要]　胞外信号调控激酶(ERK )是发现的第1个丝裂原活化蛋白激酶(MAPK ),它调控多种重要的细胞生

物学过程,包括细胞增殖、分化和凋亡等。ERK 信号级联反应能够特异地介导广泛的生物学过程,其机制主要是通过信号的反馈调控,与支架蛋白的相互作用,亚细胞定位的改变,在级联反应的每一个环节存在不同功能的多种组分,细胞内非磷酸酶抑制物和G 蛋白等的调控实现的。

[关键词]　激酶;　亚细胞定位;　支架蛋白;　信号调控

[中图分类号]　R392.4 [文献标识码]　A [文章编号]　167322588(2009)0120015205

Regul a tory m echan is m s of ERK si gna l tran sducti on pa thway

Z HAO M ingzhe

1,2

,L IU J inghua 2,L I Yuhua 1,J I A NG Yong

2

(1.L aboratory of D evelop m ental B iology,School of L ife Science,N ortheast Forestry U niversity,Harbin 150040;

2.Guang D ong Provincial Key Laboratory of Functional P roteo m ics,Southern M edical U niversity,Guangzhou 510515,China )

[Abstract]　Extracellular signal 2regulated kinase (ERK ),the first m it ogen 2activated p r otein ki 2nase (MAPK )t o be identified,contr ols many kinds of i m portant cell bi ol ogical p r ocesses,such as cell p r oliferati on,differentiati on,apop t osis and more .MAPK signal cascade s pecificully regulates vari ous bi o 2l ogical p r ocesses,the mechanis m s of which including regulati on by feedback l oop s,interacti on with s pe 2cific scaffold p r oteins,changes in subcellular l ocalizati on,p resence of multi p le components with distinct functi ons in each tier of the cascade,nonphos phatase inhibit ors of ERK signaling and G p r otein .

[Key words]　kinase;　subcellular l ocalizati on;　scaff old p r otein;　signal regulati on

[I nt J Pathol Clin Med,2009,29(1):0015205]

丝裂原活化蛋白激酶(m it ogen 2activated p r otein kinase,MAPK )是真核生物中广泛存在的一类丝氨酸/苏氨酸蛋白激酶。在哺乳动物中已经发现了4种不同的MAPK,它们分别是胞外信号调控激酶(extracellular signal 2regulated kinase,ERK )、c 2Jun N 末端激酶(c 2Jun N 2ter m inal kinase,JNK )、p38丝裂原活化蛋白激酶(p38m it ogen 2activated p r otein ki 2nase,p38)和胞外信号调控激酶5(extracellular sig 2nal 2regulated kinase 5,ERK5)。MAPK 级联反应一

般由3至5个环节组成:丝裂原活化蛋白4激酶(m it ogen 2activated p r otein 4kinase,MAP4K )、丝裂原活化蛋白3激酶(MAP3K )、丝裂原活化蛋白2激酶(MAP2K )、MAPK 和MAPK 活化蛋白激酶(MAPK 2activating p r otein kinase,MAPK APK ),其中MAP3K,

MAP2K 和MAPK 是级联反应的中心(图1)[1]

。受

到刺激后MAP3K 磷酸化MAP2K 的Ser/Thr 残基并将其激活,双重特异性磷酸激酶MAP2K 磷酸化MAPK 的Thr/Tyr 残基并将其激活

[2]

。与其他

5

1