Reactome | RHEB in mTORC1:RHEB:GTP hydrolyses GTP

RHEB in mTORC1:RHEB:GTP hydrolyses GTP

Stable Identifier

R-HSA-380979

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol, lysosomal membrane

ReviewStatus

5/5

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TSC2 (in the TSC complex) functions as a GTPase-activating protein and stimulates the intrinsic GTPase activity of the small G-protein Rheb. This results in the conversion of Rheb:GTP to Rheb:GDP. GDP-bound Rheb is unable to activate mTOR (Inoki et al. 2003, Tee et al. 2003). It is not demonstrated that RHEB hydrolyzes GTP when present in the mTORC1 complex; given the low affinity of RHEB for mTOR, it may dissociate from the mTORC1 complex before TSC2 stimulates hydrolysis of GTP; TSC2 may not have access to critical residues of RHEB when present inside mTORC1.

Literature References

PubMed ID	Title	Journal	Year
12906785	Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb Tee, AR, Manning, BD, Cantley, LC, Blenis, J, Roux, PP	Curr Biol	2003
12869586	Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling Inoki, K, Guan, KL, Li, Y, Xu, T	Genes Dev	2003