Actions of PP2A on the MAP kinase pathway and apoptosis are mediated by distinct regulatory subunits

Proceedings of the National Academy of Sciences of the United States of America
Adam M SilversteinMarc C Mumby

Abstract

Individual subunits of protein phosphatase 2A (PP2A), protein phosphatase 4, and protein phosphatase 5 were knocked out in Drosophila Schneider 2 cells by using RNA interference. Ablation of either the scaffold (A) or catalytic (C) subunits of PP2A caused the disappearance of all PP2A subunits. Treating cells with double-stranded RNA targeting all four of the Drosophila PP2A regulatory subunits caused the disappearance of both the A and C subunits. The loss of PP2A subunits was associated with decreased protein stability indicating that only the heterotrimeric forms of PP2A are stable in intact cells. Ablation of total PP2A by using double-stranded RNA against either the A or C subunit, or specific ablation of the R2/B regulatory subunit, enhanced insulin-induced ERK activation. These results indicated that the R2/B subunit targets PP2A to the mitogen-activated protein (MAP) kinase cascade in Schneider 2 cells, where it acts as a negative regulator. A severe loss of viability occurred in cells in which total PP2A or both isoforms of the Drosophila R5/B56 subunit had been ablated. The reduced viability of these cells correlated with the induction of markers of apoptosis including membrane blebbing and stimulation of caspase-3-li...Continue Reading

References

Jul 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·W H Biggs, S L Zipursky
Mar 1, 1990·Trends in Biochemical Sciences·P CohenY Tsukitani
Nov 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·M F MoranT Pawson
Nov 9, 1995·Biochimica Et Biophysica Acta·B T Gjertsen, S O Døskeland
Nov 14, 1997·The Biochemical Journal·S KloekerB E Wadzinski
May 28, 1998·The Journal of Biological Chemistry·M F SantoroD A Giegel
Jul 21, 1998·The Journal of Biological Chemistry·Z Baharians, A H Schönthal
Apr 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J P ThièryJ L Misset
Jun 22, 1999·Current Biology : CB·C P Hunter
Jul 10, 1999·The Journal of Biological Chemistry·P P RuvoloW S May
Aug 26, 1999·Trends in Genetics : TIG·A Fire
Sep 1, 1999·Proceedings of the National Academy of Sciences of the United States of America·R ShtrichmanT Kleinberger
Dec 1, 1999·Cell Death and Differentiation·K E FladmarkS O Døskeland
Mar 14, 2000·Current Opinion in Cell Biology·D M Virshup
May 10, 2000·The Journal of Biological Chemistry·D AbrahamM Baccarini
May 24, 2000·Proceedings of the National Academy of Sciences of the United States of America·J C ClemensJ E Dixon
Jan 4, 2001·Cell Death and Differentiation·S Kumar, J Doumanis
Mar 15, 2001·Current Opinion in Cell Biology·R W Carthew

❮ Previous
Next ❯

Citations

Aug 5, 2010·Osteoporosis International : a Journal Established As Result of Cooperation Between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA·Y J WeiS C Hung
Aug 30, 2011·Apoptosis : an International Journal on Programmed Cell Death·Ujwal Mukund MahajanKulbhushan Tikoo
Jan 24, 2008·Cancer Metastasis Reviews·Danilo Perrotti, Paolo Neviani
Apr 18, 2013·Nature Communications·Li JiangYongna Xing
Mar 23, 2005·Nature Methods·Douglas B WheelerDavid M Sabatini
Nov 22, 2005·Oncogene·Jason D Arroyo, William C Hahn
Dec 11, 2002·The European Journal of Neuroscience·Karsten SchmidtJürgen Götz
Dec 5, 2009·Proceedings of the National Academy of Sciences of the United States of America·Shyue-fang Battaglia-HsuJean-Louis Guéant
Aug 29, 2007·The Journal of Biological Chemistry·Jocelyn A Lee, David C Pallas
Apr 10, 2008·The Journal of Biological Chemistry·Anthony J DavisMarc C Mumby
Oct 30, 2008·The Journal of Biological Chemistry·Vivian R RuvoloPeter P Ruvolo
Oct 15, 2008·The Journal of Biological Chemistry·Renae K BarrStuart M Pitson
Oct 22, 2002·Molecular Biology of the Cell·Matthew S Gentry, Richard L Hallberg
Feb 10, 2009·Cardiovascular Research·Melanie MarshallAlison C Cave
May 1, 2013·Human Molecular Genetics·Ivelisse SánchezAntoni Matilla-Dueñas
Mar 3, 2012·Journal of Biochemistry·Dipali DateWilliam R Taylor
May 4, 2013·Nucleic Acids Research·Lei ZhouChristophe Carles
Mar 21, 2009·Molecular Pharmacology·Jamie L McConnell, Brian E Wadzinski
Apr 11, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Nicole D GlaserTerry B Rogers
Dec 17, 2010·Cancer Research·Anna A SablinaWilliam C Hahn
Jan 25, 2005·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Natsuko NakadaEi Kawahara
Apr 24, 2008·The Journal of Clinical Investigation·Rodger E TiedemannA Keith Stewart
Apr 2, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jonathan L BrigmanAndrew Holmes
Nov 23, 2011·The Journal of Endocrinology·Kai Wang, Jing Zheng
Mar 21, 2007·Proceedings of the National Academy of Sciences of the United States of America·Rubaiyat Rahman-RoblickKlas G Wiman

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis