定向迁移细胞前沿Rac局部化激活的分子调控  

Regulation of Localized Rac Activation in Leading Edge of Directed Migrating Cells

作　　者：李友军[1] 罗孝勇[1] 郭向荣[1] 

机构地区：[1]湖南师范大学生命科学学院分子细胞实验室,中国长沙410081

出　　处：《湖南师范大学自然科学学报》2013年第1期63-67,共5页Journal of Natural Science of Hunan Normal University

基　　金：国家自然科学基金资助项目(81172051);湖南省自然科学基金重点资助项目(10JJ2014)

摘　　要：提出构想:当α4胞内区域磷酸化而抑制其与paxillin结合时,paxillin、GIT1与PIX、PAK形成信号分子复合物.由于PIX为Rac的转换分子,PAK为Rac的效应分子,构成了paxillin-GIT1-PIX-PAK信号转导通路,从而促使Rac在细胞前沿持续地局部化激活,导致片状足的形成,产生细胞向前扩展推动力.研究结果表明,GIT1与paxillin、PIX在活细胞中均存在强烈的相互作用,且这种相互作用可发生在细胞前沿.由于Rac的转换因子PIX(PAK-interacting exchange factor)在活细胞中往往与PAK相伴而行,因而,在细胞前沿,必定存在paxillin-GIT1-PIX-PAK的信号转导通路.在纤粘蛋白(fibronectin)刺激下,整合素α4诱导Rac蛋白处于激活状态(GTP-bound).Rac activation is strongly regulated spacially and temporally in migrating cells, leading to the formation of specific cell protrusion-lamellipodia in leading edge of the ceils and generating the pushing force to put the cells forward, but the molecular mechanism of positive regulation of localized Rac activation remains unclear. We propose that the phosphorylation of the intracellular a4 integrin inhibits the interaction of a4 with paxillin, thus the signaling pathway paxillin-GIT1-PIX-PAK would be formed, leading to localized Rac activation in leading edge of the migrating cells. In the paper, western blotting clearly showed that the interactions accurately exist between the cytoskeleton proteins GIT1 and paxillin or PIX respectively. Fluorescent colocalization confirmed that the interactions between GIT1 and paxillin or PIX occur in the leading edge of the cells. Rac activation assay elucidated that Rac is in activated state （GTP-bound） under the stimulation of ECM fibronectin, suggesting that the way tion signaling pathpaxillin-GIT1-PIX-PAK led to Rac activation. The results built the experimental basis for the study of regula mechanism on localized Rac activation in leading edge of directed migrating cells.

关 键 词：paxillin-GIT1-PIX-PAK信号转导通路 Rac蛋白激活 免疫印迹 免疫荧光 

分 类 号：Q26[生物学—细胞生物学]