RHEB in mTORC1:RHEB:GTP hydrolyses GTP

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
SVG |   | PPTX  | SBGN
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout

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
Catalyst Activity

GTPase activity of Active mTORC1 complex [lysosomal membrane]

This event is regulated