title: Biphasic myosin II light chain activation during clot retraction.
abstract: Clot retraction is an essential step during primary haemostasis, thereby promoting thrombus stability and wound healing. Integrin αIIbβ3 plays a critical role in clot retraction, by inducing acto-myosin interactions that allow platelet cytoskeleton reorganisation. However, the signalling pathways that lead to clot retraction are still misunderstood. In this study, we report the first data on the kinetics of myosin II light chain (MLC) phosphorylation during clot retraction. We found an early phosphorylation peak followed by a second peak. By using specific inhibitors of kinases and small G proteins, we showed that MLC kinase (MLCK), RhoA/ROCK, and Rac-1 were involved in clot retraction and in the early MLC phosphorylation peak. Only Rac-1 and actin polymerisation, controlled by outside-in signalling, were crucial to the second MLC phosphorylation peak.
authors: Dr Christilla Bachelot-Loza, INSERM UMR_S U765, Université Paris Descartes, Faculté de Pharmacie, 4 avenue de l'Observatoire, 75006 Paris, France, Tel : +33 153739619, E-mail: christilla.bachelot-loza@parisdescartes.fr.
authors: Marion
authors: M
authors: Egot
authors: Alexandre
authors: A
authors: Kauskot
authors: Dominique
authors: D
authors: Lasne
authors: Pascale
authors: P
authors: Gaussem
authors: Christilla
authors: C
authors: Bachelot-Loza
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D000205:Actomyosin / Q000378:metabolism; D000577:Amides / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D001381:Azepines / Q000494:pharmacology; D001792:Blood Platelets / Q000502:physiology*; D002478:Cells, Cultured; D003018:Clot Retraction / Q000502:physiology; D006801:Humans; D007700:Kinetics; D018994:Myosin Light Chains / Q000378:metabolism*; D024462:Myosin Type II / Q000378:metabolism*; D009219:Myosin-Light-Chain Kinase / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism*; D011725:Pyridines / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects; D014945:Wound Healing; D020830:rac1 GTP-Binding Protein / Q000037:antagonists & inhibitors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000577:Amides; D000634:Aminoquinolines; D001381:Azepines; D018994:Myosin Light Chains; C487513:NSC 23766; D009281:Naphthalenes; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011725:Pyridines; D011743:Pyrimidines; C070571:ML 7; C108830:Y 27632; D000205:Actomyosin; D054460:rho-Associated Kinases; D009219:Myosin-Light-Chain Kinase; D024462:Myosin Type II; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein
keywords: Clot retraction; cytoskeleton; kinases; myosin light chain; signal transduction