RHEB in mTORC1:RHEB:GTP hydrolyses GTP

Stable Identifier
R-HSA-380979
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
12869586 Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling

Inoki, K, Li, Y, Xu, T, Guan, KL

Genes Dev 2003
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, Roux, PP, Cantley, LC, Blenis, J

Curr Biol 2003
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
GTPase activity of Active mTORC1 complex [lysosomal membrane]
Physical Entity
Activity
This event is regulated
Orthologous Events
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Created