What RHEB?

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. RHEB is a recently discovered member of the Ras superfamily.

How does RHEB activate mTORC1?

This indicates that RHEB activates mTORC1 by allosterically realigning active-site residues, bringing them into the correct register for catalysis. To confirm this, we compared the steady-state kinetic constants of S6K1367–404 phosphorylation by mTORC1 in the presence of 250 μM RHEB–GTPγS or RHEB–GDP.

Is RHEB an oncogene?

Constitutively active, GTP-bound Rheb has oncogenic potential; it transforms primary avian cells in culture and imparts on these cells the ability of anchorage-independent growth.

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.

What does RHEB do to mTOR?

Rheb plays critical roles in the activation of mTOR, a serine/threonine kinase that is involved in the activation of protein synthesis and growth. We also describe a protocol for rapamycin treatment, which directly inhibits mTOR and can be used to investigate the mTOR signaling pathway in cell growth, cell size, etc.

What is the mTOR gene?

The MTOR gene provides instructions for making a protein called mTOR. This protein is found in various cell types throughout the body including brain cells. It interacts with other proteins to form two distinct protein groups, called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2).

How is RHEB activated?

Rheb in its GTP-bound state interacts with mTORC1 and activates it. This involves enhanced recruitment of substrate proteins resulting in their phosphorylation.

What chromosome is rhoa on?

RHOA (ras homolog gene family, member A)

What is Rac1 in biology?

Ras-related C3 botulinum toxin substrate 1 (Rac1) is a member of the RAS superfamily of small GTPases. It plays an essential role in control of the cell polarity, actin cytoskeleton rearrangements, protein trafficking and directed motility in a vide variety of mammalian cells [1], [2].

Does RHEB inhibit mTOR?

We show that Rheb regulates mTOR through FKBP38, a member of the FK506-binding protein (FKBP) family that is structurally related to FKBP12. FKBP38 binds to mTOR and inhibits its activity in a manner similar to that of the FKBP12-rapamycin complex.

What do GTPases do?

3.2. 1 Introduction. Small GTPases are enzymes that catalyze the hydrolysis of guanosine triphosphate (GTP) to guanosine diphosphate (GDP). As the most well-known members, Ras GTPases play essential roles in regulating cell growth, cell differentiation, cell migration, and lipid vesicle trafficking.

Is Rheb localized on the Golgi but not on the lysosome?

However, the intracellular localization of Rheb is controversial. In this study, we showed that a significant portion of Rheb is localized on the Golgi but not on the lysosome. GFP-Rheb could activate mTORC1, even when forced to exclusively localize to the Golgi.

What is the role of RHEB in the activation of cells?

RHEB acts as an activator for mTORC1 in its GTP-bound form, therefore GTP -bound RHEB activates cell growth and proliferation within the cell. RHEB can serve as a regulator, for other proteins independent from mTORC1.

What is the role of the lysosome in metabolism?

After decades of being known as just the cellular recycling center, the lysosome has recently emerged as a central hub for metabolic signaling. Signaling pathways that call the lysosome home connect this organelle to key anabolic and catabolic processes that control many facets of cellular metabolism.

Where is mTORC1 activated in the lysosome?

In response to amino acid supply, mTORC1, a master regulator of cell growth, is recruited to the lysosome and activated by the small GTPase Rheb. However, the intracellular localization of Rheb is controversial. In this study, we showed that a significant portion of Rheb is localized on the Golgi bu …