title: Characterisation of Rac activation in thrombin- and collagen-stimulated human blood platelets.
abstract: In this study, we characterised the mechanisms of Rac GTPase activation in human platelets stimulated by two physiological agonists, either thrombin, acting through membrane receptors coupled to heterotrimeric G-proteins, or collagen which is known to mobilise a tyrosine kinase-dependent pathway. Both agonists induced a rapid activation of Rac that was not significantly affected by the inhibition of integrin alpha(IIb)beta(3) engagement. Using pharmacological inhibitors, we found that phospholipase C activation and calcium mobilisation were essential for platelet Rac activation by either thrombin or collagen whereas protein kinase C inhibition was without effect. In contrast to Rac, Cdc42 activation was independent of phospholipase C activation, indicating that the two GTPases are differently regulated. We also found that phosphoinositide 3-kinase was not required for Rac activation in response to thrombin but was involved in its activation by collagen.
authors.affiliation: Institut Fédératif de Recherche Claude de Préval, INSERM Unité 326, Hôpital Purpan, Toulouse, France.
authors.forename: C
authors.initials: C
authors.lastname: Soulet
authors.forename: S
authors.initials: S
authors.lastname: Gendreau
authors.forename: K
authors.initials: K
authors.lastname: Missy
authors.forename: V
authors.initials: V
authors.lastname: Benard
authors.forename: M
authors.initials: M
authors.lastname: Plantavid
authors.forename: B
authors.initials: B
authors.lastname: Payrastre
mesh_terms: D001596:Benzylamines; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D003094:Collagen / Q000378:metabolism / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011760:Pyrrolidinones / Q000494:pharmacology; D013844:Thiazoles; D013917:Thrombin / Q000378:metabolism / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000187:drug effects / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism*
chemical_list: D001596:Benzylamines; D002118:Calcium; D002867:Chromones; D003094:Collagen; D004791:Enzyme Inhibitors; D011464:Epoprostenol; D004963:Estrenes; D007211:Indoles; D009025:Morpholines; D009842:Oligopeptides; D019869:Phosphatidylinositol 3-Kinases; D010880:Piperidines; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases; D011760:Pyrrolidinones; D013844:Thiazoles; D013917:Thrombin; D010738:Type C Phospholipases; D020764:cdc42 GTP-Binding Protein; D054462:p21-Activated Kinases; D020744:rac GTP-Binding Proteins; C106774:SR 121566; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C046617:arginyl-glycyl-aspartyl-serine; C515903:PAK1 protein, human; C064758:Ro 31-8220