What is mTORC1 and mTORC2?

What is mTORC1 and mTORC2?

mTOR forms two multiprotein complexes, mTORC1 and mTORC2 which are composed of discrete protein binding partners to regulate cell growth, motility, and metabolism. These complexes are sensitive to distinct stimuli, as mTORC1 is sensitive to nutrients while mTORC2 is regulated via PI3K and growth factor signaling.

What is mTORC1 pathway?

Pathway Description: The first, mTOR complex 1 (mTORC1), is composed of mTOR, Raptor, GβL, and DEPTOR and is inhibited by rapamycin. It is a master growth regulator that senses and integrates diverse nutritional and environmental cues, including growth factors, energy levels, cellular stress, and amino acids.

Is mTORC2 a kinase?

The mammalian target of rapamycin (mTOR), a protein kinase, is the centre of huge attention due to its importance in intracellular signaling and in health and disease.

What is the function of mTORC1?

mTORC1 is best known for its function in promoting translation initiation and protein synthesis by directly phosphorylating ribosomal protein S6 kinases (S6Ks) and eIF4E-binding proteins (4E-BPs). Additional mTORC1 targets include regulatory proteins with roles in cell signalling, metabolism and autophagy.

Which function is controlled by mTORC2?

Glutamine and ROS metabolism mTORC2 controls glutamine uptake by regulating the cell surface amino acid transporters, SNAT2 and LAT1, through AKT and SGK activation73,74. This complex also up regulates glutaminase levels to promote glutaminolysis through c-Myc52.

How does mTORC2 activate Akt?

The initiating step in Akt activation is the binding of PIP3 to the pleckstrin homology (PH) domain of Akt, and subsequent translocation of Akt to the plasma membrane, where it is activated by phosphorylation through PDK1 [1 -3] and by PDK2 which has been shown to be the mTOR complex 2 (mTORC2) [4].

What is mTORC2?

mTOR Complex 2 (mTORC2) is an acutely rapamycin-insensitive protein complex formed by serine/threonine kinase mTOR that regulates cell proliferation and survival, cell migration and cytoskeletal remodeling. The complex itself is rather large, consisting of seven protein subunits.

What signal is required for mTORC1?

Activation of mTORC1, which is composed of mTOR, Raptor, mLST8, PRAS40, and DEPTOR, depends on the Rag and Rheb GTPases, and requires signals from amino acids, glucose, oxygen, energy (ATP), and growth factors (including cytokines and hormones such as insulin).

What regulates mTORC1?

mTOR, as the catalytic subunit of two distinct protein complexes, mTORC1 and mTORC2, is the major regulator of growth in animals and controls most anabolic and catabolic processes in response to nutrients and nutrient-induced signals, like insulin (Fig.

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.

Are there any effectors or substrates of mTORC2 signaling?

While mTORC1 signaling is well characterized, mTORC2 is relatively poorly understood. mTORC2 appears to exist in functionally distinct pools, but few mTORC2 effectors/substrates have been identified. Here, we review recent advances in our understanding of mTORC2 signaling, with particular emphasis on factors that control mTORC2 activity.

What is the role of mTORC2 in cell growth?

While mTORC1 signaling is well characterized, mTORC2 is relatively poorly unde … Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase and a master regulator of cell growth and metabolism, forms two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2.

Which is the signaling target of rapamycin mTORC2?

Regulation of mTORC2 Signaling Mammalian target of rapamycin (mTOR), a serine/threonine protein kinase and a master regulator of cell growth and metabolism, forms two structurally and functionally distinct complexes, mTOR complex 1 (mTORC1) and mTORC2. While mTORC1 signaling is well characterized, mTORC2 is relatively poorly unde …

How is mTORC2 related to PI3K upstream signaling?

Upstream signaling Similar to other PI3K regulated proteins, mTORC2 has a mSin1 subunit, which contains a phosphoinositide-binding PH domain. This domain is vital for the insulin-dependent regulation of mTORC2 activity and inhibits the catalytic activity of mTORC2 in the absence of insulin.