Phosphorylation of the activation loop of gamma p21-activated kinase (gamma-Pak) and related kinases (MSTs) in normal and stressed neutrophils

The Journal of Immunology : Official Journal of the American Association of Immunologists
J P LianJohn A Badwey

Abstract

Neutrophils stimulated with a variety of chemoattractants exhibit a rapid activation of two p21-activated kinases (Paks) with molecular masses of approximately 63 and 69 kDa (gamma- and alpha-Pak). A number of in vitro studies suggest that modification of Thr(402) in the activation loop (AL) of gamma-Pak can play a critical role in the regulation of this kinase under certain circumstances. A phosphospecific Ab was generated to this region of Pak (pPak(AL)Ab). This Ab reacted with activated gamma- and alpha-Pak from fMLP-stimulated neutrophils that contain the sequence KRXT(P)XXGTP in their ALS: The rapid but transient activation of Paks in normal stimulated neutrophils coincided with phosphorylation and dephosphorylation at the ALs of these enzymes. In contrast, stressed cells exhibited a prolonged phosphorylation at Thr(402) in both intact gamma-Pak and a proteolytic fragment of this kinase. The pPak(AL)Ab also reacted with the mammalian sterile twenty-like kinases (MSTs) (members of the Pak family) in osmotically stressed neutrophils and neutrophils treated with certain apoptotic agents (i.e., tumor promoters that inhibit type 1 and 2A protein phosphatases) but not in normal fMLP-stimulated cells. Thus, our results indicate t...Continue Reading

References

Jan 1, 1986·Methods in Enzymology·J A Badwey, M L Karnovsky
Dec 8, 1995·The Journal of Biological Chemistry·P D BurbeloA Hall
Sep 15, 1995·The Journal of Biological Chemistry·C L Creasy, J Chernoff
Sep 17, 1996·Proceedings of the National Academy of Sciences of the United States of America·L K TaylorR L Erikson
Nov 14, 1997·The Journal of Biological Chemistry·K Schinkmann, J Blenis
Feb 12, 1998·Proceedings of the National Academy of Sciences of the United States of America·N LeeL T Williams
Nov 13, 1998·Science·M H CardoneJ C Reed
Dec 22, 1998·Molecular and Cellular Biology·H Tu, M Wigler
Mar 13, 1999·The Journal of Biological Chemistry·A GattiJ A Traugh
Sep 2, 1999·Trends in Biochemical Sciences·R H Daniels, G M Bokoch
Dec 23, 1999·Current Biology : CB·G H RenkemaK Saksela
Jan 5, 2000·Proceedings of the National Academy of Sciences of the United States of America·J P MiraU G Knaus
Mar 14, 2000·Molecular and Cellular Biology·O T FacklerB M Peterlin
Apr 5, 2000·The Journal of Biological Chemistry·C C KingG M Bokoch
Apr 26, 2000·The Journal of Biological Chemistry·J A FrostM H Cobb
Jan 3, 2001·The Journal of Cell Biology·M A SellsJ Chernoff
Apr 1, 1997·Trends in Cell Biology·M A Sells, J Chernoff

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Citations

Jan 5, 2011·The Journal of Biological Chemistry·Cai GuoGerd P Pfeifer
Dec 18, 2013·The Journal of Clinical Investigation·Lisa E S CroseCorinne M Linardic
Sep 23, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qian ZhanJohn A Badwey
Sep 12, 2002·The Journal of Biological Chemistry·Helmut GlantschnigAlfred A Reszka
Jan 8, 2008·Science in China. Series C, Life Sciences·JinJun Wang, ZhiXin Wang
Oct 29, 2003·Journal of Immunological Methods·Taisuke OhiraJohn A Badwey

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