Rheb

Gene/Protein · 8 studies in the Atlas

Small GTPase that directly activates mTORC1 when in its GTP-bound state; held inactive by TSC1/TSC2.

Evidence at a glance

TierWhat it meansStudies
DMechanistic / in vitro / review8

No direct human evidence in the Atlas for this entity yet — everything below rests on animal or mechanistic work.

Studies

StudyYearTierFinding
SAN20102010DEstablished WHERE mTORC1 gets switched on: the lysosome surface. Identified Ragulator as the lysosomal dock that recruits the Rag GTPases and drags mTORC1 to the membrane where its activator Rheb live
SAN20072007DIdentified PRAS40 as the missing insulin-controlled brake INSIDE mTORC1. When insulin is absent PRAS40 clamps the complex shut; insulin makes Akt phosphorylate PRAS40, releasing the brake so Rheb can
LON20052005DRheb binds the mTOR kinase domain and directly stimulates its activity.
GAR20032003DInsulin activates Rheb-GTP, inhibited by TSC1/2, positioning Rheb as the direct upstream activator of TOR.
INOK20032003DTSC2 is a GAP for Rheb; loss of TSC2 raises Rheb-GTP and constitutively activates mTOR.
SAU20032003DRheb promotes cell growth as a component of the insulin/TOR network in Drosophila.
STO20032003DRheb is an essential regulator of S6K controlling cell growth downstream of TSC in Drosophila.
TEE20032003DTSC1-TSC2 acts as a GTPase-activating protein (GAP) for Rheb; when TSC is inactive, Rheb accumulates in its active GTP-bound form and directly activates mTORC1.

Related entities

mTORC1 3Akt/PKB 1TSC1/TSC2 1Raptor 1Rag GTPases 1Lysosome 1Ragulator 1PRAS40 1

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