中南大学湘雅医学院,中南大学生命科学学院/遗传学国家重点实验室
湖南省百人计划资助项目(2015-ZSD)
XiangYa School of Medicine , Central South University,School of Life Sciences, State key laboratory of Medical Genetics, Central South University
This work was supported by a grant from Hunan Provincial Recruitment Program(2015-ZSD)
Src蛋白激酶在人类多种肿瘤细胞中被激活并在肿瘤发生、发展过程中起重要作用.Src活性的调节主要包括共价修饰、异构调节,但基因突变和其他一些方式也可以调节其活性.Src共价修饰主要是磷酸化,Tyr530、Tyr419、Thr34、Thr46、Ser72、Tyr138和Tyr213等都是Src的磷酸化位点,其中Tyr530位点和Tyr419位点是Src最重要的磷酸化位点.异构调节包括SH3、SH2等区域结合的调节,分别涉及黏着斑激酶(focal adhesion kinase,FAK)、孕酮受体(progesterone receptor,PR)、雌激素受体(estrogen receptor,ER)、雄激素受体(androgen receptor,AR)、P130Cas、血小板源生长因子(the platelet-derived growth factor,PDGF)、血小板衍生生长因子受体(platelet-derived growth factor receptor,PDGFR)、表皮生长因子受体(epidermal growth factor receptor,EGFR,HER1/erbB1)、人类表皮生长因子受体2(human epidermal growth factor receptor-2,ERBB2/HER2/NEU)、胰岛素样生长因子1受体(insulin-like growth factor -1 receptor,IGF-1R)、纤维母细胞生长因子受体1(fibroblast growth factor receptor,FGFR1)、肝细胞生长因子受体(hepatocyte growth factor receptor c-Met)、人类1型T细胞白血病病毒编码的辅助蛋白p13、HIV-1毒力因子Nef和Sin.本文就Src蛋白激酶的调节机制作一简要综述.
The tyrosine kinase Src is activated in a large number of human malignancies and plays significant roles in the development of cancers. Activation of Src in human cancers employs a variety of mechanisms mainly including covalent modification, allosteric regulation, gene mutation. Covalent modifications of Src mainly include phosphorylation and oxidization. Tyr530, Tyr419, Thr34, Thr46, Ser72, Tyr138 and Tyr213 are phosphorylation sites of Src, among which Tyr530 and Tyr419 are the most important ones. Allosteric regulations of Src involve its regulatory Src homology 3 (SH3) or SH2 domains,which interacts with allosteric regulators, such as FAK, PR, ER, AR, P130Cas, PDGF, PDGFR, EGFR, HER2, IGF-1R, FGFR-1, c-Met, p13, Nef and Sin. In this review, we summarize the key mechanisms regulating Src kinase activity in cancer cells.
胡睿,朱曙东. Src蛋白激酶活性的调节机制[J].生物化学与生物物理进展,2016,43(11):1061-1069
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