支架蛋白Gab2信号调控与乳腺癌

Gab2是支架蛋白Gabs家族中的重要成员.该家族蛋白通过介导膜受体与信号转运蛋白间的偶联及各信号分子间的整合参与信号传导.作为支架蛋白,Gab2可被酪氨酸激酶磷酸化激活,接受胞外多种因子刺激,招募富含SH2结构域的信号转运分子,活化下游SHP2/Ras/ERK和PI3K/AKT等一系列信号传导途径,在细胞增殖、分化、...

Gab2 Signaling in Breast Cancer

Gab2 is a key member of growth factor receptor-bound protein 2 (Grb2) associated binder (Gab) family proteins, which transduces cellular signals between receptors and intracellular downstream effectors, and provide platforms for protein interactions. As a scaffolding adaptor, Gab2 is usually activated by protein-tyrosine kinases (PTKs), integrating signals from a wide variety of extracellular stimuli. When phosphorylated by PTKs, Gab2 recruits several SH2 domain-containing proteins, and subsequently triggers various downstream signal events, such as SHP2/Ras/ERK and PI3K/AKT, playing an important role in cell growth, differentiation, apoptosis and migration. Recently it has been reported that Gab2 is overexpressed in some primary mammary tumors and human breast cancer cell lines. Gab2 mediated molecular events have been closely associated with mammary tumorigenesis and metastasis, in coordination with oncogenic activities (ErbB2/Neu etc.). This review mainly focuses on the structure, involvement in signal transduction of Gab2 protein and its regulation in breast cancer.