The growth factor receptor-bound protein 2 (Grb2)-associated binder (Gab) proteins are intracellular scaffolding/docking molecules, and participate in multiple signaling pathways, usually acting as the downstream effector of protein-tyrosine kinases (PTKs)-triggered signal transduction pathway. When phosphorylated by PTKs, Gab proteins can recruit several signaling molecules (p85, SHP2, and Crk), and subsequently activate multiple transmitting signals that are critical for cell growth, survival, differentiation and apoptosis. Recently, it has been reported that Gab2 polymorphism is associated with the increase in the risk of Alzheimer's disease (AD) and is involved in the pathogenesis of AD. This review mainly focuses on the structure and function of Gab2 protein and its role in the pathogenesis of AD.
作为一类骨架/接头蛋白, 生长因子受体结合蛋白2 (Grb2)的相关结合蛋白家族(Grb2-associated binder protein) 参与了细胞内多种信号转导通路, 是酪氨酸激酶(PTKs)激活的下游信号转导通路的关键分子。 Gab2是这个家族的重要成员, 可被PTKs 磷酸化激活, 进而招募多种信号分子(如p85、 SHP2 和Crk), 在细胞增殖、 存活、 分化和凋亡等过程中发挥重要作用。 最近研究表明, Gab2 基因多态性可增加阿尔茨海默病(Alzheimer’s disease, AD)的患病风险, 从而与AD的发病密切相关。 本文拟对Gab2 的结构特点、 相关信号转导通路及其在AD发生过程中可能扮演的角色作一系统综述。