The function study on the interaction between Grb2 and AMPK.

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.