Structure and function of Gab2 and its role in cancer (Review).
Structure and function of Gab2 and its role in cancer (Review).
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DOI：
10.3892/mmr.2015.3951
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发表时间：
2015-09
影响因子：
3.4
通讯作者：
Luo JM
中科院分区：
文献类型：
--
作者：
Ding CB;Yu WN;Feng JH;Luo JM
GRB相关结合蛋白(Gab)家族的对接蛋白在受体和细胞内下游效应物之间传递细胞信号，为蛋白质相互作用提供平台。Gab2是Gab蛋白家族的重要成员，在多种细胞外刺激下参与信号转导的扩增和整合，包括生长因子、细胞因子和抗原受体。Gb2蛋白缺乏内在的催化活性；然而，当被蛋白酪氨酸激酶(PTKs)磷酸化时，Gb2招募了几个含有Src Homology-2(SH2)结构域的蛋白，包括含有Sh2的蛋白酪氨酸磷酸酶2(SHP2)、磷脂酶C-γ(PLCγ)1、Crk和GC-GAP。通过这些相互作用，Gab2蛋白可激活多种下游信号效应因子，包括SHP2/大鼠肉瘤病毒癌基因/RAF/丝裂原活化蛋白激酶/细胞外信号调节激酶和PI3K/AKT，参与细胞的生长、分化、迁移和凋亡。已有研究表明，Gab2和/或Gab2信号的异常与人类肿瘤的发生密切相关，特别是在乳腺癌、白血病和黑色素瘤中。本文就Gab2基因的结构和功能、在肿瘤中的作用及其作为有效治疗靶点的潜力作一综述。
The docking proteins of the Grb-associated binder (Gab) family transduce cellular signals between receptors and intracellular downstream effectors, and provide a platform for protein-protein interactions. Gab2, a key member of the Gab family of proteins, is involved in the amplification and integration of signal transduction, evoked by a variety of extracellular stimuli, including growth factors, cytokines and antigen receptors. Gab2 protein lacks intrinsic catalytic activity; however, when phosphorylated by protein-tyrosine kinases (PTKs), Gab2 recruits several Src homology-2 (SH2) domain-containing proteins, including the SH2-containing protein tyrosine phosphatase 2 (SHP2), the p85 subunit of phosphoinositide-3 kinase (PI3K), phospholipase C-γ (PLCγ)1, Crk, and GC-GAP. Through these interactions, the Gab2 protein triggers various downstream signal effectors, including SHP2/rat sarcoma viral oncogene/RAF/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase and PI3K/AKT, involved in cell growth, differentiation, migration and apoptosis. It has been previously reported that aberrant Gab2 and/or Gab2 signaling is closely associated with human tumorigenesis, particularly in breast cancer, leukemia and melanoma. The present review aimed to focus on the structure and effector function of Gab2, its role in cancer and its potential for use as an effective therapeutic target.