Aug 1, 2003 · Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR.

Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR.

RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle. [5] RHEB is a recently discovered member of the Ras superfamily.

Studies over the years have established Rheb as a member of the Ras superfamily G-proteins. This G-protein has unique structural features and has a high GTP level. TSC1/TSC2 complex functions as a GAP for Rheb and this involves the use of the asparagine-thumb mechanism.

Rheb is a unique member of the Ras superfamily GTPases. Structural characterization of Rheb revealed a number of important features of this GTPase. TSC1/TSC2/TBC1D7 has been established as a GAP for Rheb and its GAP activity appears to use the Asn-thumb mechanism similar to the RapGAP proteins.

Rheb and TSC2 comprise a unique pair of GTPase and GAP, because Rheb has high basal GTP levels and TSC2 does not have the catalytic arginine finger found in Ras-GAP. To investigate the function of TSC2 and Rheb in mTOR signaling, we analyzed the …

The intrinsic rate of GTP hydrolysis by Rheb is slow, but it is substantially accelerated when Rheb interacts with the GTPase-activating protein (GAP) domain of tuberous sclerosis complex 2 (TSC2); when GTP is hydrolyzed to GDP, Rheb is inactivated.

2 days ago · TSC2 inhibits mTORC1 with dual roles as both a GAP and a potential guanine nucleotide dissociation inhibitor for Rheb; it promotes GTP hydrolysis of Rheb, and then binds the resulting inactive GDP ...

Structural and biochemical analyses reveal TSC2 GAP-Rheb complimentary interactions and suggest a catalytic mechanism, by which an asparagine thumb (N1643) stabilizes γ-phosphate of GTP and accelerate GTP hydrolysis of Rheb.

May 27, 2003 · Here we show that the small GTPase Rheb (Ras homologue enriched in brain) is a direct target of Tsc2 GAP activity both in vivo and in vitro. Point mutations in the GAP domain of Tsc2 disrupted...