Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3'-kinase.

Abstract : Platelet-activating factor (PAF), a potent inflammatory mediator, is involved in endothelial permeability. This study was designed to characterize PAF receptor (PAF-R) expression and its specific contribution to the modifications of adherens junctions in mouse endothelial cells. We demonstrated that PAF-R was expressed in mouse endothelial cells and was functionally active in stimulating p42/p44 MAPK and phosphatidylinositol 3-kinase (PtdIns3'-kinase)/Akt activities. Treatment of cells with PAF induced a rapid time- and dose-dependent (10(-7) to 10(-10) M) increase in tyrosine phosphorylation of a subset of proteins ranging from 90 to 220 kDa, including the VE-cadherin, the latter effect being prevented by the tyrosine kinase inhibitors herbimycin A and bis-tyrphostin. We demonstrated that PAF promoted formation of multimeric aggregates of VE-cadherin with PtdIns3'-kinase, which was also inhibited by herbimycin and bis-tyrphostin. Finally, we show by immunostaining of endothelial cells VE-cadherin that PAF dissociated adherens junctions. The present data provide the first evidence that treatment of endothelial cells with PAF promoted activation of tyrosine kinases and the VE-cadherin tyrosine phosphorylation and PtdIns3'-kinase association, which ultimately lead to the dissociation of adherens junctions. Physical association between PtdIns3'-kinase, serving as a docking protein, and VE-cadherin may thus provide an efficient mechanism for amplification and perpetuation of PAF-induced cellular activation.
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FASEB Journal, Federation of American Society of Experimental Biology, 2005, 19 (6), pp.512-20. 〈10.1096/fj.04-2202com〉
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Hélène Hudry-Clergeon, Dominique Stengel, Ewa Ninio, Isabelle Vilgrain. Platelet-activating factor increases VE-cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3'-kinase.. FASEB Journal, Federation of American Society of Experimental Biology, 2005, 19 (6), pp.512-20. 〈10.1096/fj.04-2202com〉. 〈inserm-00433480〉

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