Oberprieler, NG; Roberts, W; Graham, AM; Homer-Vanniasinkam, S; Naseem, KM; (2007) CGMP-independent inhibition of integrin alpha(IIb)beta(3)-mediated platelet adhesion and outside-in signalling by nitric oxide. FEBS LETT , 581 (7) 1529 - 1534. 10.1016/j.febslet.2007.02.072.
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We examined the influence of S-nitrosoglutathione (GSNO) on alpha(llb)beta(3) integrin-mediated platelet adhesion to immobilised fibrinogen. GSNO induced a time- and concentration dependent inhibition of platelet adhesion. Inhibition was cGMP-independent and associated with both reduced platelet spreading and protein tyrosine phosphorylation. To investigate the cGMP-independent effects of NO we evaluated integrin beta(3) phosphorylation. Adhesion to fibrinogen induced rapid phosphorylation of beta(3) on tyrosines 773 and 785, which was reduced by GSNO in a cGMP independent manner. Similar results were observed in suspended platelets indicating that NO-induced effects were independent of spreading-induced signalling. This is the first demonstration that NO directly regulates integrin beta(3) phosphorylation. (c) 2007 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.
|Title:||CGMP-independent inhibition of integrin alpha(IIb)beta(3)-mediated platelet adhesion and outside-in signalling by nitric oxide|
|Keywords:||nitric oxide, platelets, cGMP, integrin alpha(IIb)beta(3), tyrosine phosphorylation, PROTEIN-TYROSINE KINASE, ACTIVATION, AGGREGATION, PHOSPHORYLATION, RECEPTORS|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)|
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