Characterisation of Rac activation in thrombin- and collagen-stimulated human blood platelets.
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.
Soulet
C
C
Institut Fédératif de Recherche Claude de Préval, INSERM Unité 326, Hôpital Purpan, Toulouse, France.
Gendreau
S
S
Missy
K
K
Benard
V
V
Plantavid
M
M
Payrastre
B
B
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*
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