Regulation of an activated S6 kinase 1 variant reveals a novel mammalian target of rapamycin phosphorylation site.

The Journal of Biological Chemistry
Masao SaitohG Thomas

Abstract

A critical step in S6 kinase 1 (S6K1) activation is Thr(229) phosphorylation in the activation loop by the phosphoinositide-dependent protein kinase (PDK1). Thr(229) phosphorylation requires prior phosphorylation of the Ser/Thr-Pro sites in the autoinhibitory domain and Thr(389) in the linker domain, consistent with PDK1 more effectively catalyzing Thr(229) phosphorylation in a variant harboring acidic residues in these positions (S6K1-E389D(3)E). S6K1-E389D(3)E has high basal activity and exhibits partial resistance to rapamycin and wortmannin, and its activity can be further augmented by mitogens, effects presumably mediated by Thr(229) phosphorylation. However, PDK1-induced Thr(229) phosphorylation is reported to be constitutive rather than phosphatidylinositide 3,4,5-trisphosphate-dependent, suggesting that S6K1-E389D(3)E activity is mediated through a distinct site. Here we use phosphospecific antibodies to show that Thr(229) is fully phosphorylated in S6K1-E389D(3)E in the absence of mitogens and that regulation of S6K1-E389D(3)E activity by mitogens, rapamycin, or wortmannin parallels Ser(371) phosphorylation. Consistent with this observation, a dominant interfering allele of the mammalian target of rapamycin, mTOR, inhi...Continue Reading

References

Aug 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·S FerrariG Thomas
Oct 5, 1995·Nature·E J BrownS L Schreiber
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·Q P WengJ Avruch
May 13, 1993·Nature·H A LaneG Thomas
Sep 6, 1996·The Journal of Biological Chemistry·A D KohnR A Roth
May 30, 1997·The Journal of Biological Chemistry·K ReifD A Cantrell
Jun 23, 1997·FEBS Letters·N Pullen, G Thomas
Sep 1, 1997·Molecular and Cellular Biology·B A MoserG Thomas
Feb 21, 1998·Science·N PullenG Thomas
Mar 21, 1998·Proceedings of the National Academy of Sciences of the United States of America·P E BurnettD M Sabatini
Oct 8, 1998·The Biochemical Journal·K AkimotoS Ohno
Feb 18, 1999·Current Biology : CB·C BelhamJ Avruch
Mar 11, 1999·Current Opinion in Genetics & Development·P B DennisG Thomas
Sep 25, 1999·Science·J MontagneG Thomas
Nov 24, 1999·The Journal of Biological Chemistry·S IsotaniK Yonezawa
May 18, 2001·Nature·P Blume-Jensen, T Hunter

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Citations

Sep 27, 2002·Genesis : the Journal of Genetics and Development·Hélène Barcelo, Mary J Stewart
Aug 10, 2005·The International Journal of Biochemistry & Cell Biology·David J Glass
Aug 21, 2003·Trends in Molecular Medicine·David J Glass
Nov 9, 2011·Proceedings of the National Academy of Sciences of the United States of America·Sejeong ShinSang-Oh Yoon
Oct 25, 2008·The Journal of Biological Chemistry·Tomohiko MaehamaKentaro Hanada
Dec 11, 2008·The Journal of Biological Chemistry·Wei ChenMelanie H Cobb
Nov 1, 2003·Molecular Biology of the Cell·Amy K A deHartLinda Hicke
Dec 12, 2003·Science's STKE : Signal Transduction Knowledge Environment·Thurl E Harris, John C Lawrence
Mar 10, 2005·Microbiology and Molecular Biology Reviews : MMBR·Ken InokiKun-Liang Guan
Jun 10, 2010·Critical Reviews in Eukaryotic Gene Expression·Hongyu Zhou, Shile Huang
Apr 7, 2011·Experimental & Molecular Medicine·Chang Hoon Cho
Oct 10, 2003·Proceedings of the National Academy of Sciences of the United States of America·Chang-Hyuk KwonSuzanne J Baker
Apr 11, 2012·EMBO Molecular Medicine·Sandra GoebbelsKlaus-Armin Nave
Dec 21, 2005·FEBS Letters·Jin-Jing PeiBengt Winblad
Jan 17, 2015·Nutrients·Galia Gat-Yablonski, Moshe Phillip
Oct 11, 2011·Critical Reviews in Biochemistry and Molecular Biology·Bing Su, Estela Jacinto
Nov 20, 2015·Molecular Biology of the Cell·Amra SaricRoberto J Botelho
Oct 11, 2011·Pediatric Clinics of North America·Galia Gat-YablonskiMoshe Phillip
Sep 1, 2009·Endocrinology and Metabolism Clinics of North America·Galia Gat-YablonskiMoshe Phillip
Jul 22, 2008·Journal of Theoretical Biology·Catherine KellyMichael Brady
Jul 28, 2005·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·R J Seeley, D A York
Jan 27, 2011·Journal of Cellular Biochemistry·Marc-Olivier FrégeauGaétan Guillemette
Apr 13, 2013·International Journal of Cancer. Journal International Du Cancer·Anja MüllerChristian W Scholz
Mar 20, 2010·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Kanako KumeHiroshi Handa
Dec 8, 2004·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Janet E Lindsley, Jared Rutter
Jun 15, 2004·Biochemical Pharmacology·T L FreemanM E Mailliard
Mar 26, 2016·IEEE Journal of Selected Topics in Quantum Electronics : a Publication of the IEEE Lasers and Electro-optics Society·Bernard ChoiJ Stuart Nelson
Jul 23, 2014·Asian-Australasian Journal of Animal Sciences·Wu ManlinWang Zhigang

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