Dec 21, 2017 · The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTOR …

A number of studies establish that one of the functions of Rheb is to activate mTOR leading to growth. In particular, the ability of Rheb to activate mTORC1 in vitro points to direct interaction of Rheb with the mTORC1 complex.

Dec 13, 2017 · It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras...

Apr 26, 2005 · Genetic evidence establishes that TOR complex activity in vivo requires the small GTPase Rheb, and overexpression of Rheb can rescue TOR from inactivation in vivo by amino-acid withdrawal. The Tuberous Sclerosis heterodimer (TSC1/TSC2) functions as a Rheb GTPase activator and inhibits TOR signaling in vivo.

Rheb plays critical roles in the activation of mTOR, a serine/threonine kinase that is involved in the activation of protein synthesis and growth. mTOR forms two distinct complexes, mTORC1 and mTORC2.

Jul 1, 2011 · mTOR exists in two distinct complexes. mTOR complex 1 (mTORC1) is potently inhibited by the immunosupressive macrolide rapamycin; whereas, mTORC2 is insensitive to this durg. These mTOR complexes play an integral role in the regulation of many cellular processes including protein synthesis, autophag …

Apr 26, 2005 · The ability of nucleotide-free Rheb to bind in vitro to purified mTOR 2148–2549 is consistent with the ability of the nucleotide-deficient Rheb mutants Ser20Asn and Asp60Ile to bind full-length mTOR and the mTOR 2148–2549 fragment in …

Nov 9, 2007 · Our findings suggest that FKBP38 is an endogenous inhibitor of mTOR, whose inhibitory activity is antagonized by Rheb in response to growth factor stimulation and nutrient availability.

Feb 7, 2018 · Here, we report the discovery of a small molecule (NR1) that binds Rheb in the switch II domain and selectively blocks mTORC1 signaling. NR1 potently inhibits mTORC1 driven phosphorylation of...

Here we present the 3.0 Å cryo-EM structure of mTORC1 and the 3.4 Å structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis.