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. Author manuscript; available in PMC: 2015 Mar 4.
Published in final edited form as: Cell Metab. 2014 Feb 6;19(3):373–379. doi: 10.1016/j.cmet.2014.01.001

Figure 3.

Figure 3

(A) Many negative feedback loops in mTOR signaling. When mTORC1 is active, Akt activation is attenuated by inhibition of the RTK-PI3K signaling pathway through multiple mechanisms including inhibitory phosphorylation events on IRS by mTORC1 or S6K1 and Rictor by S6K1, and stimulation of inhibitory adaptor protein Grb10 by mTORC1. (B) Rapamycin relieves negative feedback loops and promotes activation of PI3K signaling. The inhibition of mTORC1 by rapamycin reduces the mTORC1-driven negative feedback effects, and thus activates the PI3K-Akt pathway and promotes cell survival. Additionally, partial inhibition of mTORC1 substrates by rapamycin such as 4E-BP1 may also contribute to cell survival.