Activation of p38 MAP-kinase and caldesmon phosphorylation are essential for urokinase-induced human smooth muscle cell migration.

Biological Chemistry
Elena A GoncharovaV A Tkachuk

Abstract

We have explored intracellular pathways involved in the urokinase type plasminogen activator (urokinase or uPA)-stimulated migration of human airway smooth muscle cells (hAWSMC). Using a set of uPA mutants we found that protease activity, growth factor-like and kringle domains of uPA differentially contribute to activation of p42/p44erk1,2 and p38 MAP-kinases. Consistent with our earlier data [Mukhina et al., J. Biol. Chem. 275 (2000), 16450-16458], the kringle domain of uPA was sufficient and required to stimulate cell motility. Here we report that uPA mutants containing the kringle domain specifically activate the p38 MAP-kinase pathway and actomyosin by increasing phosphorylation of the critical Ser-19 on the myosin regulatory light chain and MAP-kinase sites of the actin-associated regulatory protein caldesmon. While pharmacological inhibition of p38 MAP-kinase activation did not affect myosin light chain phosphorylation, it blocked the increase in caldesmon phosphorylation and uPA-stimulated migration of hAWSMC on a collagen-coated surface. We conclude that activation of p38 MAP-kinase and downstream phosphorylation of non-muscle caldesmon is essential for urokinase-stimulated smooth muscle cell migration.

References

Dec 4, 1992·Annals of the New York Academy of Sciences·C L Jackson, M A Reidy
Apr 1, 1987·The Journal of Investigative Dermatology·S MoriokaP J Jensen
Oct 13, 1995·The Journal of Biological Chemistry·S ZhangG M Bokoch
Sep 1, 1996·Clinical and Experimental Pharmacology & Physiology·V TkachukA Bobik
Apr 21, 1997·The Journal of Cell Biology·R L KlemkeD A Cheresh
Feb 7, 1998·The Journal of Biological Chemistry·I DumlerD C Gulba
Feb 7, 1998·Science·A Hall
Mar 5, 1999·Journal of Neuro-oncology·T J MacDonaldW E Laug
Aug 14, 1999·The Journal of Biological Chemistry·J C HedgesW T Gerthoffer
Oct 8, 1999·Molecular Biology of the Cell·D M HelfmanA D Bershadsky
Mar 18, 2000·Biochemical and Biophysical Research Communications·A V SomlyoA P Somlyo
Feb 7, 2001·American Journal of Physiology. Cell Physiology·J C HedgesW T Gerthoffer
Jun 29, 2000·Annual Review of Biochemistry·K KaibuchiM Amano
May 30, 2001·FEBS Letters·E A GoncharovaA V Vorotnikov

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Citations

May 2, 2006·Clinical & Experimental Metastasis·Crispin R DassPeter F M Choong
Feb 3, 2006·Journal of Biomedical Science·Jolanta KordowskaChih-Lueh Albert Wang
Jul 27, 2007·Molecular Therapy : the Journal of the American Society of Gene Therapy·Dmitry O TraktuevYelena V Parfyonova
Jan 6, 2012·Journal of Allergy·Annaïg OzierPatrick Berger
Feb 26, 2003·American Journal of Respiratory Cell and Molecular Biology·Elena A GoncharovaReynold A Panettieri
Jan 3, 2006·American Journal of Respiratory Cell and Molecular Biology·Elena A GoncharovaVera P Krymskaya
Jun 25, 2003·American Journal of Respiratory Cell and Molecular Biology·J Mark Madison
Mar 14, 2008·Blood·Victoria StepanovaDouglas B Cines
Aug 10, 2010·The European Respiratory Journal·F LiK F Chung
May 2, 2007·The European Respiratory Journal·S S AnL Wang
Dec 21, 2007·Proceedings of the American Thoracic Society·William T Gerthoffer
Apr 17, 2009·Canadian Journal of Physiology and Pharmacology·Vsevolod A TkachukYelena V Parfyonova
Mar 18, 2006·Clinics in Chest Medicine·Aili L Lazaar, Reynold A Panettieri
Aug 17, 2004·The Journal of Allergy and Clinical Immunology·Michael I KotlikoffPrescott G Woodruff
Aug 17, 2004·The Journal of Allergy and Clinical Immunology·Stuart J HirstAlastair G Stewart
Sep 24, 2005·Pulmonary Pharmacology & Therapeutics·Alaina J Ammit
Feb 26, 2011·Cell Adhesion & Migration·Taira Mayanagi, Kenji Sobue
Dec 6, 2011·Atherosclerosis·Bianca Fuhrman
Jun 22, 2016·European Journal of Cell Biology·Ekaterina SeminaVsevolod Tkachuk
Apr 8, 2009·International Review of Cell and Molecular Biology·Jim Jung-Ching LinJian-Ping Jin
Oct 12, 2004·American Journal of Physiology. Lung Cellular and Molecular Physiology·Talaibek BorbievAlexander D Verin
Aug 11, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Sheng LiKazuhiro Kohama
Dec 26, 2006·American Journal of Physiology. Lung Cellular and Molecular Physiology·Neil HendersonSimon Richard Johnson
Mar 15, 2003·The Journal of Biological Chemistry·Yoshihiko YamakitaFumio Matsumura
Dec 25, 2010·Molecular and Cellular Biochemistry·Wilson K C LeungNathalie Wong
Jan 31, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Qing WangJianying Zhou
Sep 17, 2004·Journal of Cell Science·Cai HuangMichael D Schaller
Nov 3, 2004·Journal of Cellular Physiology·Tamara MirzapoiazovaAlexander D Verin

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