Pan Zhi, Wang Jian, Yin Xiushan, Xie Ping, Yang Juntao, Jiang Jizhi, Zhang Lingqiang, He Fuchu
State Key Laboratory of Proteomics, Beijing Proteomics Research Center, Beijing Institute of Radiation Medicine, Beijing, China.
Mol Cell Biochem. 2008 Jan;307(1-2):121-7. doi: 10.1007/s11010-007-9591-6. Epub 2007 Sep 12.
Growth factor receptor-bound protein 2 (Grb2) is an extensively studied adaptor protein involved in cell signaling. Grb2 is a highly flexible protein composed of a single SH2 domain flanked by two SH3 domains. The evolutionarily conserved serine/threonine kinase, AMP-activated protein kinase (AMPK), functions as a cellular fuel gauge that regulates metabolic pathways in glucose and fatty acid metabolism and protein synthesis. AMPK regulates the activation of TSC2 by phosphorylating TSC2. Here we report for the first time on the interaction of Grb2 with AMPK. SH2 domain of Grb2 and KIS domain of AMPK are both required for the combination of Grb2 and AMPK. Furthermore, Grb2 function as a factor which mediates phosphorylation of AMPK at Thr172, and potentially involves in metabolism pathways and AMPK-TSC2-mTOR cell growth pathway through regulating the activation of AMPK.
生长因子受体结合蛋白2（Grb2）是一种参与细胞信号传导且被广泛研究的衔接蛋白。Grb2是一种高度灵活的蛋白质，由一个位于两个SH3结构域之间的单个SH2结构域组成。进化上保守的丝氨酸/苏氨酸激酶，即AMP活化蛋白激酶（AMPK），作为一种细胞能量传感器，调节葡萄糖和脂肪酸代谢以及蛋白质合成中的代谢途径。AMPK通过磷酸化TSC2来调节TSC2的激活。在此，我们首次报道了Grb2与AMPK之间的相互作用。Grb2的SH2结构域和AMPK的KIS结构域都是Grb2与AMPK结合所必需的。此外，Grb2作为介导AMPK在Thr172位点磷酸化的因子，并可能通过调节AMPK的激活参与代谢途径以及AMPK-TSC2-mTOR细胞生长途径。
