Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation - PubMed (original) (raw)
. 1999 Dec 1;344 Pt 2(Pt 2):427-31.
Affiliations
- PMID: 10567225
- PMCID: PMC1220660
Mammalian target of rapamycin is a direct target for protein kinase B: identification of a convergence point for opposing effects of insulin and amino-acid deficiency on protein translation
B T Navé et al. Biochem J. 1999.
Abstract
Growth factor induced activation of phosphoinositide 3-kinase and protein kinase B (PKB) leads to increased activity of the mammalian target of rapamycin (mTOR). This subsequently leads to increased phosphorylation of eIF4E binding protein-1 (4EBP1) and activation of p70 ribosomal S6 protein kinase (p70(S6K)), both of which are important steps in the stimulation of protein translation. The stimulation of translation is attenuated in cells deprived of amino acids and this is associated with the attenuation of 4EBP1 phosphorylation and p70(S6K) activation. It has been suggested that PKB regulates mTOR function by phosphorylation although direct phosphorylation of mTOR by PKB has not been demonstrated previously. In the present work, we have found that PKB directly phosphorylates mTOR and, using phosphospecific antibodies, we have shown this phosphorylation occurs at Ser(2448). Insulin also induces phosphorylation on Ser(2448) and this effect is blocked by wortmannin but not rapamycin, consistent with the effect being mediated by PKB. Amino-acid starvation rapidly attenuated the reactivity of the Ser(2448) phosphospecific antibody with mTOR and this could not be restored by either insulin stimulation of cells or incubation with PKB in vitro. Our findings demonstrate that mTOR is a direct target for PKB and support the conclusion that regulation of phosphorylation of Ser(2448) is a point of convergence for the counteracting regulatory effects of growth factors and amino acid levels.
Similar articles
- A direct linkage between the phosphoinositide 3-kinase-AKT signaling pathway and the mammalian target of rapamycin in mitogen-stimulated and transformed cells.
Sekulić A, Hudson CC, Homme JL, Yin P, Otterness DM, Karnitz LM, Abraham RT. Sekulić A, et al. Cancer Res. 2000 Jul 1;60(13):3504-13. Cancer Res. 2000. PMID: 10910062 - Acetaldehyde promotes rapamycin-dependent activation of p70(S6K) and glucose uptake despite inhibition of Akt and mTOR in dopaminergic SH-SY5Y human neuroblastoma cells.
Fang CX, Yang X, Sreejayan N, Ren J. Fang CX, et al. Exp Neurol. 2007 Jan;203(1):196-204. doi: 10.1016/j.expneurol.2006.08.002. Epub 2006 Sep 7. Exp Neurol. 2007. PMID: 16962100 - TOR action in mammalian cells and in Caenorhabditis elegans.
Long X, Müller F, Avruch J. Long X, et al. Curr Top Microbiol Immunol. 2004;279:115-38. doi: 10.1007/978-3-642-18930-2_8. Curr Top Microbiol Immunol. 2004. PMID: 14560955 Review. - [mTOR, the mammalian target of rapamycin].
Julien LA, Roux PP. Julien LA, et al. Med Sci (Paris). 2010 Dec;26(12):1056-60. doi: 10.1051/medsci/201026121056. Med Sci (Paris). 2010. PMID: 21187044 Review. French.
Cited by
- Adaptive protein synthesis in genetic models of copper deficiency and childhood neurodegeneration.
Lane AR, Scher NE, Bhattacharjee S, Zlatic SA, Roberts AM, Gokhale A, Singleton KS, Duong DM, McKenna M, Liu WL, Baiju A, Moctezuma FGR, Tran T, Patel AA, Clayton LB, Petris MJ, Wood LB, Patgiri A, Vrailas-Mortimer AD, Cox DN, Roberts BR, Werner E, Faundez V. Lane AR, et al. bioRxiv [Preprint]. 2024 Sep 12:2024.09.09.612106. doi: 10.1101/2024.09.09.612106. bioRxiv. 2024. PMID: 39314281 Free PMC article. Preprint. - Unveiling the Mechanism of Protective Effects of Tanshinone as a New Fighter Against Cardiovascular Diseases: A Systematic Review.
Dabbaghi MM, Soleimani Roudi H, Safaei R, Baradaran Rahimi V, Fadaei MR, Askari VR. Dabbaghi MM, et al. Cardiovasc Toxicol. 2024 Sep 22. doi: 10.1007/s12012-024-09921-x. Online ahead of print. Cardiovasc Toxicol. 2024. PMID: 39306819 Review. - Protein phosphatase 4 maintains the survival of primordial follicles by regulating autophagy in oocytes.
Dong MZ, Ouyang YC, Gao SC, Gu LJ, Guo JN, Sun SM, Wang ZB, Sun QY. Dong MZ, et al. Cell Death Dis. 2024 Sep 8;15(9):658. doi: 10.1038/s41419-024-07051-4. Cell Death Dis. 2024. PMID: 39245708 Free PMC article. - FOXC1 transcriptionally suppresses ABHD5 to inhibit the progression of renal cell carcinoma through AMPK/mTOR pathway.
Li J, Chen S, Xiao J, Ji J, Huang C, Shu G. Li J, et al. Cell Biol Toxicol. 2024 Aug 2;40(1):62. doi: 10.1007/s10565-024-09899-w. Cell Biol Toxicol. 2024. PMID: 39093497 Free PMC article. - Ubiquitin specific protease 38 aggravates pathological cardiac remodeling by stabilizing phospho-TBK1.
Xiao Z, Dai C, Yu T, Zhu J, Pan Y, Shuai W, Kong B, Huang H. Xiao Z, et al. Int J Biol Sci. 2024 Feb 25;20(5):1815-1832. doi: 10.7150/ijbs.85562. eCollection 2024. Int J Biol Sci. 2024. PMID: 38481817 Free PMC article.
References
- J Biol Chem. 1996 Nov 22;271(47):30199-204 - PubMed
- EMBO J. 1996 Oct 1;15(19):5256-67 - PubMed
- FEBS Lett. 1996 Dec 16;399(3):333-8 - PubMed
- J Biol Chem. 1997 Mar 21;272(12):7713-9 - PubMed
- Curr Biol. 1997 Apr 1;7(4):261-9 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials
Miscellaneous