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. Author manuscript; available in PMC: 2016 Sep 1.
Published in final edited form as: Nat Cell Biol. 2016 Feb 8;18(3):319–327. doi: 10.1038/ncb3311

Figure 5.

Figure 5

mTORC1 orchestrates feedback inhibition of IGF-1 signaling by promoting HIF1α-dependent expression of IGFBP5. IGFBP5 accumulates in the extracellular space, and sequesters IGF-1 from binding to its cognate receptor (IGF-1R). mTORC1 also inhibits IGF-1 signaling by upregulating the expression of Grb10, and downregulating the expression of IRS and IGF-1R. Both Grb10 and IGFBP5 are potential tumor suppressors. Conversely, IGF-1R and PI3K is activated in mTORC1-suppressed conditions (e.g. rapamycin-treated), due to the relief of mTORC1-mediated feedback inhibition loops. Red and gray indiate proteins that are in the activated and repressed states, respectively.