PLATELET-ACTIVATING-FACTOR (PAF) INDUCES THE EARLY TYROSINE PHOSPHORYLATION OF FOCAL ADHESION KINASE (P125(FAK)) IN HUMAN ENDOTHELIAL-CELLS

Citation
R. Soldi et al., PLATELET-ACTIVATING-FACTOR (PAF) INDUCES THE EARLY TYROSINE PHOSPHORYLATION OF FOCAL ADHESION KINASE (P125(FAK)) IN HUMAN ENDOTHELIAL-CELLS, Oncogene, 13(3), 1996, pp. 515-525
Citations number
67
Categorie Soggetti
Oncology,Biology,"Cell Biology
Journal title
ISSN journal
09509232
Volume
13
Issue
3
Year of publication
1996
Pages
515 - 525
Database
ISI
SICI code
0950-9232(1996)13:3<515:P(ITET>2.0.ZU;2-L
Abstract
Platelet-activating factor (PAF) is a potent activator of angiogenesis and controls the motility and the shape of vascular endothelium. The mechanism(s) whereby PAF exerts its action are in part known. Here we report that the biological active (R)PAF enantiomer administrated to c ultured endothelial cells induces the early phosphorylation in tyrosin e residues of focal (p125(FAK)) and paxillin, two molecules early sign aling and cytoskeleton assembly in cells that undergo integrin-mediate d adhesion or are challenged by neuropeptides or lysophosphatidic acid . The phenomenon is rapidly turned on, lasts for a few minutes and is adhesion-independent indicating that the chain of events induced by (R )PAF, including p125(FAK) activation, precedes adhesion. The inhibitor y effect of WEB2086, a PAF receptor antagonist, and the lack of activi ty exerted by the (S)PAF enantiomer, indicate that (R)PAF-mediated p12 5(FAK) activation, is PAF receptor-dependent. Calphostin C, an inhibit or of protein kinase C blocks the effect of (R)PAF on p125(FAK); phosp horylation suggesting that protein kinase C activation is up-stream th e activation of this tyrosine kinase. When endothelial cells are expos ed to a substratum that allows adhesion and spreading. (R)PAF-stimulat ed cells, change their adhesive phenotype and start migrating. Inhibit ors of tyrosine kinases, like 3-(1,4,-dihydroxytetralyl) methy-len-2-o xindole and herbimycin A, reduce the cells migration, the transendothe lial flux of albumin and the enhancement of p125(FAK) activity induced by (R)PAF. The observation that increased tyrosine phosphorylation of p125(FAK) and its ensuing association with focal adhesion occurs rapi dly upon (R)PAF challenge indicates that this signaling molecule has a primary and independent role also in the signaling cascade initiated by (R)PAF.