What is RHEB GTPase?

What is RHEB GTPase?

Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev.

How does RHEB activates mTOR?

In response to growth factors or amino acid availability, Rheb prevents the interaction of FKBP38 with mTOR in a GTP-dependent manner, which leads to mTORC1 activation. This mechanism for the action of Rheb on mTOR is consistent with evidence that active Rheb associates less with mTOR than does the inactive form (16).

Is RHEB a kinase?

RHEB is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a serine/threonine kinase whose activation leads to phosphorylation cascades within the cell that lead to cell growth and proliferation.

What superfamily does RHEB belong to?

Rheb belongs to a unique family within the Ras superfamily of G-proteins. Although initially identified in rat brain, this G-protein is highly conserved from yeast to human.

How does TSC2 inhibit RHEB?

A proposed model of Rheb functions downstream of TSC1/TSC2 and upstream of mTOR. TSC2 acts as a GAP to inactivate Rheb by directly stimulating GTP hydrolysis. Rheb stimulates mTOR. Nutrient and cellular energy status signals through Rheb, whereas osmotic stress signals independently of Rheb.

What does the mTOR pathway do?

The mTOR signaling pathway, which is often activated in tumors, not only regulates gene transcription and protein synthesis to regulate cell proliferation and immune cell differentiation but also plays an important role in tumor metabolism.

What is rapamycin used for?

Rapamycin (Rapamune, Sirolimus) is a macrolide exhibiting potent antitumor and immunosuppressive activity [261,262]. Rapamycin is thus used in clinical settings to prevent rejection in organ transplantation and to treat certain types of cancer.

What does RHEB stand for?

Acronym. Definition. RHEB. RAS-Homolog Enriched in Brain.

Does RHEB activate mTORC2?

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.

How does mTOR regulate metabolism?

mTORC1 regulates hepatic lipid metabolism mainly through SREBP1, the master regulator of lipid synthesis. It is initially synthesized as an inactive precursor and localized in the ER. In response to the insulin signaling, SREBP1 is cleaved and transported to the nucleus to induce lipogenic gene expression.

Can rapamycin extend life?

Rapamycin may extend lifespan by postponing death from cancer, by retarding mechanisms of ageing, or both. To our knowledge, these are the first results to demonstrate a role for mTOR signalling in the regulation of mammalian lifespan, as well as pharmacological extension of lifespan in both genders.

What is a ras homolog?

Ras homolog enriched in the brain (Rheb)6 is a small GTPase belonging to the Ras superfamily of guanine nucleotide-binding proteins and is related to Ras, Rap, and Ral (1). The function of Rheb has been studied in a variety of organisms, especially in Drosophila and mammalian cells.