Rheb
Small GTPase that directly activates mTORC1 when in its GTP-bound state; held inactive by TSC1/TSC2.
The one thing that actually switches mTORC1 on.
Realigns the mTOR active site; the convergence point of the entire growth-factor arm and the reason localisation alone is not activation. Note a declared simplification in this map: Rheb is farnesylated and distributes across the endomembrane system, with a substantial ER and Golgi pool, and which pool supplies the activating Rheb is still debated. It is drawn on the lysosomal band because that is where it meets mTORC1.
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 8 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2010 | M | Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids SAN2010 Established 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 lives. Amino acids work by controlling this translocation. |
| 2007 | M | PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase SAN2007 Identified 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 fully switch mTORC1 on. Explained how hormone signals set the exact strength of mTORC1 activity. |
| 2005 | M | Rheb binds and regulates the mTOR kinase LON2005 Rheb binds the mTOR kinase domain and directly stimulates its activity. |
| 2003 | M | Tuberous sclerosis complex gene products, Tuberin and Hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb TEE2003 TSC1-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. |
| 2003 | M | Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2 GAR2003 Insulin activates Rheb-GTP, inhibited by TSC1/2, positioning Rheb as the direct upstream activator of TOR. |
| 2003 | M | Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling INOK2003 TSC2 is a GAP for Rheb; loss of TSC2 raises Rheb-GTP and constitutively activates mTOR. |
| 2003 | M | Rheb promotes cell growth as a component of the insulin/TOR signalling network SAU2003 Rheb promotes cell growth as a component of the insulin/TOR network in Drosophila. |
| 2003 | M | Rheb is an essential regulator of S6K in controlling cell growth in Drosophila STO2003 Rheb is an essential regulator of S6K controlling cell growth downstream of TSC in Drosophila. |