5wbl

Structural highlights

Function

[RTOR1_ARATH] Probable component of the plant TOR kinase pathway that recruits substrates for TOR. Modulates plant cell growth and regulates the activity of ATPK1 kinase in response to osmotic stress.^[1] [AKTS1_HUMAN] Subunit of mTORC1, which regulates cell growth and survival in response to nutrient and hormonal signals. mTORC1 is activated in response to growth factors or amino acids. Growth factor-stimulated mTORC1 activation involves a AKT1-mediated phosphorylation of TSC1-TSC2, which leads to the activation of the RHEB GTPase that potently activates the protein kinase activity of mTORC1. Amino acid-signaling to mTORC1 requires its relocalization to the lysosomes mediated by the Ragulator complex and the Rag GTPases. Activated mTORC1 up-regulates protein synthesis by phosphorylating key regulators of mRNA translation and ribosome synthesis. mTORC1 phosphorylates EIF4EBP1 and releases it from inhibiting the elongation initiation factor 4E (eiF4E). mTORC1 phosphorylates and activates S6K1 at 'Thr-389', which then promotes protein synthesis by phosphorylating PDCD4 and targeting it for degradation. Within mTORC1, AKT1S1 negatively regulates mTOR activity in a manner that is dependent on its phosphorylation state and binding to 14-3-3 proteins. Inhibits RHEB-GTP-dependent mTORC1 activation. Substrate for AKT1 phosphorylation, but can also be activated by AKT1-independent mechanisms. May also play a role in nerve growth factor-mediated neuroprotection.^{[2] [3] [4]}

References

1. ↑ Mahfouz MM, Kim S, Delauney AJ, Verma DP. Arabidopsis TARGET OF RAPAMYCIN interacts with RAPTOR, which regulates the activity of S6 kinase in response to osmotic stress signals. Plant Cell. 2006 Feb;18(2):477-90. doi: 10.1105/tpc.105.035931. Epub 2005 Dec 23. PMID:16377759 doi:http://dx.doi.org/10.1105/tpc.105.035931
2. ↑ Huang B, Porter G. Expression of proline-rich Akt-substrate PRAS40 in cell survival pathway and carcinogenesis. Acta Pharmacol Sin. 2005 Oct;26(10):1253-8. doi:, 10.1111/j.1745-7254.2005.00184.x. PMID:16174443 doi:http://dx.doi.org/10.1111/j.1745-7254.2005.00184.x
3. ↑ Vander Haar E, Lee SI, Bandhakavi S, Griffin TJ, Kim DH. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nat Cell Biol. 2007 Mar;9(3):316-23. doi: 10.1038/ncb1547. Epub 2007 Feb 4. PMID:17277771 doi:http://dx.doi.org/10.1038/ncb1547
4. ↑ Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell. 2007 Mar 23;25(6):903-15. doi: 10.1016/j.molcel.2007.03.003. PMID:17386266 doi:http://dx.doi.org/10.1016/j.molcel.2007.03.003