ERK3信号通路的活化阻止细胞增殖  

The Activation of ERK3 Signaling Pathway Blocks Cell Proliferation

作　　者：陈笛[1] 邢飞跃[1] 

机构地区：[1]暨南大学组织移植与免疫中心,广州510632

出　　处：《生物化学与生物物理进展》2007年第2期117-123,共7页Progress In Biochemistry and Biophysics

基　　金：国家自然科学基金资助项目(30471635);广东省自然科学基金资助项目(04010451;5006033);暨南大学引进优秀人才科研启动基金(51204058)~~

摘　　要：ERK3是ERK家族中结构较为独特的成员,尤其在分子生物学特征上与ERK家族其他成员明显不同,如基因结构中外显子之间的大内含子、蛋白质结构中活化环的丝氨酸单磷酸化位点以及激酶C端的延伸序列等.ERK3具有独特的丝氨酸单磷酸化位点,导致所有以苏氨酸/酪氨酸双磷酸化位点为磷酸化靶点的MEK分子均不能活化ERK3.ERK3的C端延伸序列能与细胞周期蛋白D3结合并调控ERK3的亚细胞定位,从而影响ERK3对细胞周期的调节.据目前文献推测,ERK3调控细胞周期的信号通路可能为:Ras→B-Raf→ERK3激酶→ERK3→G1期CDK复合物减少→S期抑制因子增多→细胞增殖阻滞于S期→细胞停止增殖,进入分化.此外,ERK3信号通路的活化与细胞分化、胚胎发育、胰岛素分泌以及肿瘤的发生密切相关.Extracellular signal-regulated kinase3 （ERK3） is distinguished from other ERK family members especially in its molecular biological characteristics including the big intron between exons in its gene structure, the serine 189 mono-phosphorylated site and C-terminal extention of its kinase structure. The specially activating phosphorylation site of serine189 indicates that all MEKs, which phosphorylate serine/threonine double phosphorylation sites of MAPKs, are unable to activate ERK3. The C-terminal extension involves both subcellular localization of ERK3 and binding to intact cyclin D3, which can profoundly affect cell cycle regulation. According to update reports, ERK3 signal pathway in the regulation of cell cycle might be as follows： Ras→B-Raf→ERK3kinase→ERK3→decrease of CDK compounds of Gl-phase→increase of the inhibiting factor （retinoblastoma protein） of S-phase →blockage of S-phase of cell cycle →cell differentiation entry while cell proliferation arrest. Moreover, the activation of ERK3 signaling pathway is also associated with cell differentiation, embryonic development, insulin secretion and cancer diseases.

关 键 词：细胞外信号调节激酶3 信号通路 细胞周期 

分 类 号：Q42[生物学—神经生物学]