支架蛋白Gab2与肿瘤关系的研究进展

Gab2是Gabs家族蛋白中一种至关重要的信号中介分子，该家族蛋白通过接受多种生长因子、细胞因子及抗原等胞外刺激，参与信号转导的放大及整合。Gab2蛋白被蛋白酪氨酸激酶磷酸化激活后，招募富含SH2结构域的信号效应蛋白如SHP2、 PI3K的p85亚基、Crk和GC-GAP，主要介导SHP2/RAS/ERK和PI3K/AKT两条经典的信号通路，在多种生理学及病理学过程中发挥重要作用。近年研究发现，异常的Gab2及其信号与乳腺癌、白血病及黑色素瘤等其他人类肿瘤密切相关。本文就Gab2蛋白的结构、信号调控及在肿瘤中的研究进展进行综述。

Research progress on the relationship between scaffolding adapter protein Gab2 and cancer

Growth factor receptor-bound protein 2（Grb2)-associated binding protein 2（Gab2） has emerged as a crucial signaling intermediary molecule in Gab family proteins，which is involved in the amplification and integration of signal transduction evoked by a variety of extracellular stimuli，including growth factors，cytokines，antigens，and other molecules.When phosphorylated by protein-tyrosine kinases（PTKs)，Gab2 recruits several Src homology-2（SH2） domain-containing proteins，such as SH2-containing protein tyrosine phosphatase 2（SHP2)，p85 subunit of phosphoinositide-3 kinase（PI3K)，phospholipase C-gamma 1（PLCγ)，Crk，and GC-GAP.Through these interactions，the Gab2 protein mediates the two major signal transduction pathways，the SHP2/RAS/ERK and PI3K/AKT signaling pathways，and fulfils an important if not essential role in many physiological and pathological processes.Recently it has been shown that abnormal Gab2 and its signaling have been linked to human cancer，especially in breast cancer，leukemia and melanoma.In this review，we provide a detailed overview of the structure，signaling regulation of Gab2 and its role in cancer.