Reactome | Rheb in the MTORC1 complex hydrolyses GTP

Rheb in the MTORC1 complex hydrolyses GTP

Stable Identifier

R-HSA-5672017

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal membrane

ReviewStatus

5/5

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Rheb in the MTORC1 complex hydrolyses GTP

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When cellular energy is depleted AMPK is activated and inhibits mTORC1 via phosphorylation of both TSC2 and Raptor (Gwinn et al. 2008). Phosphorylation of TSC2 increases its GAP activity on GTP-bound Rheb, enhancing the intrinsic GTPase activity of Rheb. Rheb converts its bound GTP to GDP which diminishes its stimulation of mTORC1 and thereby decreases mTORC1 kinase activity. AMPK also phosphorylates the mTORC1 component RPTOR (Raptor), which promotes its dissociation from the ULK1 complex. Both effects of AMPK lead to a reduction in S758 phosphorylation on ULK1 (Shang et al. 2011). The S758-unphosphorylated ULK1 is able to associate with, and be activated by, AMPK (Egan et al. 2011).

This event is positively regulated by the phosphorylation of the TSC complex by p-AMPK.

Literature References

PubMed ID	Title	Journal	Year
18439900	AMPK phosphorylation of raptor mediates a metabolic checkpoint Mihaylova, MM, Mery, A, Shaw, RJ, Turk, BE, Vasquez, DS, Gwinn, DM, Egan, DF, Shackelford, DB	Mol Cell	2008