Figures & data
Figure 1. Feedback regulation of PI3K/Akt/mTORC1 signaling by Grb10. Grb10 inhibits PI3K/Akt/mTORC1 pathway by binding to tyrosine phosphorylated insulin receptor (IR). Sustained activation of the mTORC1 leads to Grb10 phosphorylation at Ser501/503, which promotes Grb10 dissociation from the IR to interact with raptor, an activator of mTOR. The interaction of Grb10 with raptor prevents raptor from binding to mTOR and thus suppresses mTORC1 signaling. By phosphorylation-dependent interaction with IR and raptor, Grb10 dynamically regulates the signaling pathways downstream of IR, thus selectively regulating mTORC1-mediated biological events such as lipid metabolism, cell growth, and cell cycle.
