Protein kinase C betaII regulates Akt phosphorylation on Ser-473 in a cell type- and stimulus-specific fashion

The Journal of Biological Chemistry
Yuko KawakamiToshiaki Kawakami

Abstract

Akt (= protein kinase B), a subfamily of the AGC serine/threonine kinases, plays critical roles in survival, proliferation, glucose metabolism, and other cellular functions. Akt activation requires the recruitment of the enzyme to the plasma membrane by interacting with membrane-bound lipid products of phosphatidylinositol 3-kinase. Membrane-bound Akt is then phosphorylated at two sites for its full activation; Thr-308 in the activation loop of the kinase domain is phosphorylated by 3-phosphoinositide-dependent kinase-1 (PDK1) and Ser-473 in the C-terminal hydrophobic motif by a putative kinase PDK2. The identity of PDK2 has been elusive. Here we present evidence that conventional isoforms of protein kinase C (PKC), particularly PKCbetaII, can regulate Akt activity by directly phosphorylating Ser-473 in vitro and in IgE/antigen-stimulated mast cells. By contrast, PKCbeta is not required for Ser-473 phosphorylation in mast cells stimulated with stem cell factor or interleukin-3, in serum-stimulated fibroblasts, or in antigen receptor-stimulated T or B lymphocytes. Therefore, PKCbetaII appears to work as a cell type- and stimulus-specific PDK2.

References

Aug 9, 1996·Science·M LeitgesA Tarakhovsky
Mar 28, 1997·Science·C R BealsG R Crabtree
Jun 23, 1997·FEBS Letters·P CohenD A Cross
Feb 12, 1998·The Journal of Biological Chemistry·M AndjelkovićB A Hemmings
Sep 16, 1998·Proceedings of the National Academy of Sciences of the United States of America·M DelcommenneS Dedhar
Mar 4, 2000·The Biochemical Journal·B Vanhaesebroeck, D R Alessi
Mar 18, 2000·The Journal of Biological Chemistry·A Toker, A C Newton
Jun 15, 2000·Proceedings of the National Academy of Sciences of the United States of America·Y KawakamiT Kawakami
Sep 7, 2000·The Journal of Experimental Medicine·J KitauraT Kawakami
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·M P Scheid, J R Woodgett
Nov 10, 2001·Trends in Biochemical Sciences·D P Brazil, B A Hemmings
Dec 26, 2001·Science's STKE : Signal Transduction Knowledge Environment·T O Chan, P N Tsichlis
Aug 7, 2002·Biochemistry·Conrad P HodgkinsonGraham J Sale
Dec 24, 2002·The Biochemical Journal·Alexandra C Newton
Jul 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yuko KawakamiToshiaki Kawakami

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Citations

Jan 29, 2011·Lasers in Medical Science·Khalid M AlGhamdiNoura A Moussa
Jun 15, 2011·Apoptosis : an International Journal on Programmed Cell Death·Juraj BodoEric D Hsi
May 21, 2011·Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico·Nicholas Butowski
Mar 23, 2005·Current Opinion in Cell Biology·James R Woodgett
Mar 23, 2005·Current Opinion in Cell Biology·Matthias P Wymann, Romina Marone
Jun 23, 2007·Nature Reviews. Cancer·Helen J Mackay, Christopher J Twelves
Dec 13, 2005·Nature Reviews. Drug Discovery·Bryan T HennessyGordon B Mills
Nov 17, 2005·Oncogene·Jin Q ChengSanto V Nicosia
Aug 30, 2008·Proceedings of the National Academy of Sciences of the United States of America·Elaine HustonMiles D Houslay
Feb 16, 2012·The Journal of Biological Chemistry·Sungman ParkJin Q Cheng
Oct 25, 2006·The Journal of Experimental Medicine·Alina PatkeAlexander Tarakhovsky
Apr 5, 2012·The Journal of Experimental Medicine·Keunwook LeeMark Boothby
Nov 3, 2006·Molecular Biology of the Cell·Hisayoshi YoshizakiMichiyuki Matsuda
Aug 17, 2010·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Kostas StylianouEugene Daphnis
Mar 30, 2012·Science Signaling·Piero Dalle PezzeKathrin Thedieck
Jul 20, 2007·American Journal of Physiology. Cell Physiology·Syed J KhundmiriNicholas A Delamere
Sep 16, 2008·Molecular Cancer Therapeutics·Daruka MahadevanEmmanuelle J Meuillet
May 15, 2009·International Archives of Allergy and Immunology·Guiming LiErwin W Gelfand
Mar 25, 2010·Blood·Jia ChenRichard D Ye
Jan 1, 2010·Molecular Cancer·Boon Tin ChuaJulian Downward
Jul 5, 2013·PLoS Biology·Romy WalserMatthias P Wymann
Feb 13, 2009·Journal of the American Society of Nephrology : JASN·Dongcheng WuJoan C Krepinsky
Mar 11, 2009·Frontiers in Bioscience (Landmark Edition)·Melissa HunterClay Marsh
Mar 31, 2010·Expert Review of Hematology·Donna S Woulfe
Mar 25, 2014·Expert Opinion on Investigational Drugs·Ignace Vergote
May 22, 2008·Expert Opinion on Investigational Drugs·Yi-Bin Chen, Ann S LaCasce
Feb 6, 2016·Cell Death and Differentiation·M Gómez-SuárezP Nava
Oct 25, 2011·Cellular Signalling·Ma Eugenia DíazDaniel Turyn
Jun 17, 2015·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Akhilendra Kumar Maurya, Manjula Vinayak
Dec 13, 2005·Journal of Neurochemistry·Myriam Cordey, Christian J Pike
Sep 7, 2007·Journal of Pineal Research·Vanesa MartínCarmen Rodriguez
Sep 10, 2011·Enzyme Research·Angela BononiPaolo Pinton
Jun 7, 2005·Expert Opinion on Therapeutic Targets·Patrick M Martin, Isa M Hussaini
Aug 21, 2013·Proceedings of the National Academy of Sciences of the United States of America·Tobias V LanzMichael Platten

❮ Previous
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