What does phosphorylation of mTOR do?

The mammalian target of rapamycin (mTOR) coordinates cell growth with the growth factor and nutrient/energy status of the cell. Taken together, these results suggest that p70S6 kinase is a major effector of mTOR phosphorylation at Ser-2448 in response to both mitogen- and nutrient-derived stimuli.

Does phosphorylation activate mTOR?

The mammalian mTORC1 and mTORC2 complexes perform non-overlapping functions within the cell. The main known mTORC2 activity is the phosphorylation and activation of AKT and of the related kinases — serum/glucocorticoid regulated kinase (SGK) and protein kinase C (PKC) [35].

How does 4E BP1 inhibit translation?

The eIF4E-binding proteins (4E-BPs) are a family of three small peptides that inhibit cap-dependent translation by binding to eIF4E and obstructing its interaction with eIF4G (Lin et al.

Does mTOR inhibit 4EBP1?

INK128, an MTOR Inhibitor, Inhibits HH Signaling in the Brain The unexpected critical role of MTOR-dependent translation in HH signaling and the high p-4EBP1 levels in SHH-group medul- loblastoma in humans prompted us to investigate the potential of MTOR inhibitors in treating SHH-group medulloblastoma.

What is the role of mTOR in protein synthesis?

Signaling through mammalian target of rapamycin (mTOR) is activated by amino acids, insulin, and growth factors, and impaired by nutrient or energy deficiency. mTOR regulates numerous components involved in protein synthesis, including initiation and elongation factors, and the biogenesis of ribosomes themselves.

How is mTOR pathway regulated?

As discussed above, mTOR is regulated at multiple levels, including direct phosphorylation, oligomerization and interactions with its regulators, which in turn are controlled by an array of signaling cascades that are responsive to changes in intracellular and environmental conditions.

How do I regulate mTOR?

Energy intake, protein intake, mechanical stumuli, as well as growth factors, have been shown to regulate the mTORC1 complex. All these elements provide signals to muscle cells which are then sensed, transduced and integrated which leads to changes in cellular functions.

What is Cap dependent translation?

eIF4E
Cap-dependent translation is initiated by the binding of the factor eIF4E to the cap domain of mRNA. Detailed x-ray crystal and NMR structures are available for eIF4E in association with cap-analogs, as well as domains of other initiation factors.

Does Tor regulate phosphorylation of eIF-4E BP1 and p70 S6 kinase?

We conclude that TOR regulates the phosphorylation of both eIF-4E BP1 and the p70 S6 kinase; however, p70 is not upstream of eIF-4E BP1 but is regulated in parallel. Dulbecco’s modified Eagle’s minimal essential medium and fetal calf serum were purchased from Sigma.

Do mTOR mutants protect eIF-4E BP1 from rapamycin-induced dephosphorylation?

We show herein that such mTOR mutants also protect eIF-4E BP1 against rapamycin-induced dephosphorylation, and for both p70 S6 kinase and eIF-4E BP1, such protection requires that the rapamycin-resistant mTOR variant retains an active catalytic domain.

What is the mechanism of action of rapamycin on eIF-4E BP1 and p70 S6?

The proteins eIF-4E BP1 and p70 S6 kinase each undergo an insulin/mitogen-stimulated phosphorylation in situ that is partially inhibited by rapamycin.

What is the PMID for 4E-BP1 phosphorylation?

PMID: 10364159 Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism Anne-Claude Gingras,1Steven P. Gygi,2,3Brian Raught,1,2Roberto D. Polakiewicz,4Robert T. Abraham,5Merl F. Hoekstra,6Ruedi Aebersold,3and Nahum Sonenberg1,7