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Platelet‐activating factor increases VE‐cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3′‐kinase
Author(s) -
Hudry-Clergeon Hélène,
Stengel Dominique,
Ninio Ewa,
Vilgrain Isabelle
Publication year - 2005
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.04-2202com
Subject(s) - adherens junction , microbiology and biotechnology , tyrosine phosphorylation , tyrosine kinase , proto oncogene tyrosine protein kinase src , phosphorylation , receptor tyrosine kinase , ve cadherin , platelet activating factor , platelet derived growth factor receptor , chemistry , cancer research , biology , cadherin , signal transduction , biochemistry , endocrinology , growth factor , receptor , cell
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.—Hudry‐Clergeon, H., Stengel, D., Ninio, E., Vilgrain, I. Platelet‐activating factor increases VE‐cadherin tyrosine phosphorylation in mouse endothelial cells and its association with the PtdIns3′‐kinase. FASEB J . 19, 512–520 (2005)