Is mTOR a serine kinase?

mTOR is a serine/threonine kinase that regulates cell growth, autophagy, and the actin cytoskeleton in response to growth factor stimulation or the availability of nutrients, energy, or oxygen (11). mTOR exists in two multisubunit protein complexes, termed mTORC1 and mTORC2.

What is p70S6K function?

The 70-kDa ribosomal protein S6 kinase (p70S6K) is known to regulate cell growth by inducing protein synthesis components. We purified membrane-based p70S6K as a kinase responsible for site-specific phosphorylation of BAD, which inactivates this proapoptotic molecule.

What type of kinase is mTOR?

mTOR is considered a member of the phosphatidylinositol 3-kinase (PI3K)-kinase-related kinase superfamily since its C-terminal domain shares strong homology to the catalytic domain of PI3K [45,46]. Both mTOR complexes share the catalytic mTOR subunit, mLST8, Deptor and the Tti1/Tel2 complex.

Is mTOR a transcription factor?

mTOR controls the transcriptional activity of Pol I and III by phosphorylating TFs and regulating their activity. For e.g., in Saccharomyces cerevisiae, mTORC1 phosphorylates the TF Maf1 through S6K1, thereby controlling Pol-III mediated transcription (Wei et al., 2009).

What activates S6K?

S6K is activated by branch chain amino acids through mTOR [24, 25], and by TNF-α through IKK2 (IKKβ) [7, 9]. In those responses, S6K is shown to phosphorylate IRS-1 in the inhibition of insulin signaling pathway [6, 7].

How does mTOR get activated?

Multiple factors and pathways affect mTORC1 activity to regulate skeletal muscle mass. mTORC1 is activated by IGF-I/insulin, mechanical stimulation and amino acids (blue lines) and inhibited by glucocorticoids and myostatin (red lines). Activated mTORC1 increases protein synthesis in skeletal muscle.

What is the role of p70S6 kinase in the regulation of mTOR?

Thus, these results arguethat p70S6 kinase, rather than AKT, plays the dominant role in the regulationof mTOR phosphorylation at Ser-2448 by amino acids. Fig. 3 Amino acid stimulation increases Ser-2448 phosphorylation. HEK 293cells were grown overnight in DMEM + 10% FCS.

What is the phosphorylation of mTOR at ser-2448?

Phosphorylation of Mammalian Target of Rapamycin (mTOR) at Ser-2448 IsMediated by p70S6 Kinase* The mammalian target of rapamycin (mTOR) coordinates cell growth with thegrowth factor and nutrient/energy status of the cell. The phosphatidylinositol3-kinase-AKT pathway is centrally involved in the transmission of mitogenicsignals to mTOR.

What is the role of p70S6K in autophagy?

P70-S6 Kinase 1. The phosphorylation of p70S6K at threonine 389 has been used as a hallmark of activation by mTOR and correlated with autophagy inhibition in various situations. However, several recent studies suggest that the activity of p70S6K plays a more positive role in the increase of autophagy.

Is rapamycin activity dependent on p70 S6 kinase status?

Measurement of the mammalian target of rapamycin (mTOR) activity dependent on the phosphorylation status of p70 S6 kinase (p70 S6K) offers a practical way for monitoring pharmacodynamic drug activity, with the potential to better assess the state of immunosuppression in individual patients.