Endotoxin conditioning induces VCP/p97-mediated and inducible nitric-oxide synthase-dependent Tyr284 nitration in protein phosphatase 2A.

The Journal of Biological Chemistry
Takashi Ohama, D L Brautigan

Abstract

Endotoxins activate Toll-like receptors and reprogram cells to be refractory to secondary exposure. Here we found that activation of different Toll-like receptors elicited a time- and dose-dependent increase in the levels of the protein phosphatase 2A catalytic subunit (PP2Ac) but not its partner A subunit. We purified the lipopolysaccharide-induced form of PP2A by chromatography plus immunoprecipitation and used mass spectrometry to identify VCP/p97 as a novel partner for PP2Ac. Endogenous VCP/p97 and PP2Ac were co-immunoprecipitated from primary murine macrophages and human lymphocytes. GST-VCP/p97 bound purified PP2A in pulldown assays, showing direct protein-protein interaction. Endotoxin conditioning of macrophages induced formation of 3-nitrotyrosine in the PP2Ac associated with VCP/p97, a response severely reduced in macrophages from iNOS knock-out mice. The reaction of purified PP2A with peroxynitrite dissociated the A subunit, and 3-nitro-Tyr(284) was identified in PP2Ac by mass spectrometry. Myc-PP2Ac (Y284F) expressed in cells was resistant to peroxynitrite-induced nitration and reduction of A subunit binding. Transient expression of either VCP/p97 or PP2Ac was sufficient to elevate levels of the dual specificity pho...Continue Reading

References

Oct 6, 1997·Proceedings of the National Academy of Sciences of the United States of America·K MurataD L Brautigan
Jul 21, 1998·The Journal of Biological Chemistry·Z Baharians, A H Schönthal
Oct 15, 1998·Proceedings of the National Academy of Sciences of the United States of America·J GötzW Kues
Sep 14, 2000·Biochemistry·N E Price, M C Mumby
Mar 21, 2002·Proceedings of the National Academy of Sciences of the United States of America·Adam M SilversteinMarc C Mumby
Nov 22, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Peili ChenYusen Liu
Aug 2, 2003·Genes & Development·Deborah BranchoRoger J Davis
Aug 26, 2003·Journal of Endotoxin Research·Jian Jun GaoMaximillian T Follettie
Sep 15, 2004·The Journal of Biological Chemistry·Stefan StrackLisa Gomez
Dec 23, 2004·Shock·Marianne NimahThomas P Shanley
Jul 20, 2005·The Journal of Biological Chemistry·Jon B KleinMadhavi J Rane
Oct 15, 2005·The Journal of Clinical Investigation·Christina G KatsiariGeorge C Tsokos
Dec 29, 2005·The Journal of Experimental Medicine·Qun ZhaoYusen Liu
Mar 23, 2006·The Journal of Biological Chemistry·Franck VandermoereHubert Hondermarck
Jun 24, 2006·Molecular Cell·Dalia Halawani, Martin Latterich
Dec 19, 2006·Cell·Yanhui XuYigong Shi
Jan 12, 2008·Biochemistry·Bjarki StefanssonDavid L Brautigan
Jun 20, 2008·Journal of Proteome Research·Weifeng LuoSteven K Hanks
Mar 17, 2009·Molecular Cell·David M Virshup, Shirish Shenolikar

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Citations

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Dec 10, 2013·Mass Spectrometry Reviews·Xianquan ZhanDominic M Desiderio
Apr 28, 2016·Antioxidants & Redox Signaling·Deepika RamanShazib Pervaiz
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Oct 2, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·So Young LeeJoong-Soo Han
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