Phosphorylation of Pak1 by the p35/Cdk5 kinase affects neuronal morphology

The Journal of Biological Chemistry
T RashidMargareta Nikolić

Abstract

The small GTPase Rac and its effectors, the Pak1 and p35/Cdk5 kinases, have been assigned important roles in regulating cytoskeletal dynamics in neurons. Our previous work revealed that the neuronal p35/Cdk5 kinase associates with Pak1 in a RacGTP-dependent manner, causing hyperphosphorylation and down-regulation of Pak1 kinase activity. We have now demonstrated direct phosphorylation of Pak1 on threonine 212 by the p35/Cdk5 kinase. In neuronal growth cones, Pak1 phosphorylated on Thr-212 localized to actin and tubulin-rich areas, suggesting a role in regulating growth cone dynamics. The expression of a non-phosphorylatable Pak1 mutant (Pak1A212) induced dramatic neurite disorganization. We also observed a strong association between p35/Cdk5 and the Pak1 C-terminal kinase domain. Overall, our data show that in neurons, membrane-associated, active Pak1 is regulated by the p35/Cdk5 kinase both by association and phosphorylation, which is essential for the proper regulation of the cytoskeleton during neurite outgrowth and remodeling.

References

Oct 20, 1995·The Journal of Biological Chemistry·E ManserL Lim
Jul 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K T ShettyH C Pant
Apr 16, 1996·Proceedings of the National Academy of Sciences of the United States of America·M H LeeJ Massagué
Oct 1, 1996·Proceedings of the National Academy of Sciences of the United States of America·T OhshimaA B Kulkarni
Oct 29, 1997·Molecular and Cellular Biology·W XiongM R Rosner
Mar 1, 1997·Current Biology : CB·M A SellsJ Chernoff
Mar 28, 1998·The Journal of Biological Chemistry·R ShuangE L Stuenkel
Jun 10, 1998·The Journal of Comparative Neurology·Y T Kwon, L H Tsai
Sep 3, 1998·The Journal of Biological Chemistry·S BagrodiaR A Cerione
Sep 17, 1998·The Journal of Biological Chemistry·L J Oehlen, F R Cross
Oct 17, 1998·The Journal of Biological Chemistry·C WuM Whiteway
Dec 22, 1998·Molecular and Cellular Biology·H Tu, M Wigler
Feb 6, 1999·The Journal of Biological Chemistry·A I FletcherE L Stuenkel
Apr 15, 1999·Annual Review of Neuroscience·M E Hatten
May 20, 1999·The Journal of Cell Biology·M A SellsJ Chernoff
Jun 9, 1999·Proceedings of the National Academy of Sciences of the United States of America·Y OdaB T Chait
Aug 26, 1999·Trends in Cell Biology·S Bagrodia, R A Cerione
Sep 2, 1999·Trends in Biochemical Sciences·R H Daniels, G M Bokoch
Nov 24, 1999·The Journal of Cell Biology·W B KiossesM A Schwartz
May 8, 2000·Journal of Cellular Biochemistry·J L RosalesK Y Lee
Jun 6, 2000·Current Biology : CB·L Connell-CrowleyE Giniger
Jun 17, 2000·Results and Problems in Cell Differentiation·Y T Kwon, L H Tsai
Jul 19, 2000·Current Biology : CB·M Symons
Jul 25, 2000·Trends in Neurosciences·J G Gleeson, C A Walsh
Aug 3, 2000·Neuroreport·S HumbertL H Tsai
Feb 17, 2001·Current Opinion in Neurobiology·B J Dickson
Feb 17, 2001·Current Opinion in Neurobiology·L Redmond, A Ghosh
Mar 15, 2001·European Journal of Biochemistry·G Paglini, A Cáceres

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Citations

Jan 10, 2008·Cellular and Molecular Neurobiology·Fatema A Dhariwala, Medha S Rajadhyaksha
Jun 8, 2010·Clinical & Experimental Metastasis·Liangping YuanTobey J MacDonald
May 24, 2005·Brain Research. Molecular Brain Research·Jenny U JohanssonChristina Bark
Apr 16, 2002·The International Journal of Biochemistry & Cell Biology·Margareta Nikolic
Jul 17, 2007·Nature Neuroscience·Farahnaz SananbenesiLi-Huei Tsai
May 26, 2006·Nature Reviews. Cancer·Rakesh KumarChristopher J Barnes
Oct 23, 2002·Journal of Neurochemistry·Gary Meyer, Eva L Feldman
Dec 22, 2009·The Journal of Biological Chemistry·Yoshiaki V NishimuraTakeshi Kawauchi
Jul 25, 2008·The Journal of Biological Chemistry·Christine M LightcapJohn C Williams
Aug 19, 2007·Molecular Biology of the Cell·Frédéric CauseretMargareta Nikolic
Aug 15, 2008·Cerebral Cortex·Frédéric CauseretMargareta Nikolic
Mar 17, 2004·Molecular and Cellular Biology·Kamilah AlexanderPhilip W Hinds
Apr 5, 2003·Annual Review of Biochemistry·Gary M Bokoch
Aug 10, 2011·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·John P EggersMichael A Hollingsworth
Jul 2, 2011·Molecular Endocrinology·Jing TaoMaria Diakonova
Aug 10, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tom JacobsMargareta Nikolić
Nov 16, 2013·Journal of Molecular Neuroscience : MN·Zheng WenBo Tian
Nov 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Patrice D SmithDavid S Park
Sep 2, 2014·Journal of Physiology, Paris·André P KothDaniela M Barros
Aug 3, 2005·The Journal of Cell Biology·Tina M LeisnerLeslie V Parise
Jun 1, 2014·Molecular and Cellular Neurosciences·Yuki ItoShin-Ichi Hisanaga
Oct 23, 2012·Molecular and Cellular Neurosciences·A KumazawaT Ohshima
Mar 11, 2004·Journal of Neurochemistry·Shirley B Shelton, Gail V W Johnson
Nov 11, 2008·Annals of the New York Academy of Sciences·Estela Cecilia MlewskiGabriela Paglini
May 16, 2008·Hippocampus·Bernadett BodaDominique Muller
May 19, 2012·Cytoskeleton·Christian Gonzalez-BillaultAlfredo Caceres
Sep 8, 2004·Trends in Molecular Medicine·Patrice D SmithDavid S Park
May 31, 2015·Biochimica Et Biophysica Acta·V I PintoC A McCulloch
Jun 16, 2012·Expert Opinion on Therapeutic Patents·Wassilios G Meissner
Aug 15, 2002·Current Biology : CB·Debra A ThielJonathan Chernoff
Aug 15, 2002·Current Biology : CB·Monisha BanerjeeMargareta Nikolic
Jan 16, 2007·Cell·Ramsés AyalaLi-Huei Tsai
Sep 17, 2014·Frontiers in Aging Neuroscience·John F Castro-AlvarezGloria P Cardona-Gómez

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