Tyrosine phosphorylation of pp125FAK and paxillin in aortic endothelial cells induced by mechanical strain.
The objective of this study was to determine whether focal adhesion proteins pp125FAK (focal adhesion kinase) and paxillin are phosphorylated on tyrosine and might play a role in the morphological change and cell migration induced by strain. Bovine aortic endothelial cells (EC) were subjected to 10% average strain at 60 cycles/min. Cyclic strain increased the tyrosine phosphorylation of pp125FAK at 30 min (3.4-fold) and 4 h (5.9-fold) and the tyrosine phosphorylation of paxillin at 4 h (2.0-fold). Confocal microscopy showed that, after 4-h exposure to strain, EC began to elongate and F-actin, pp125FAK, and paxillin aligned, although they randomly distributed in static condition. Tyrosine kinase inhibitor tyrphostin A25 (100 microM) inhibited not only the tyrosine phosphorylation of pp125FAK and paxillin but also the redistribution of pp125FAK and paxillin, morphological change, and migration of EC induced by strain. These data demonstrate that cyclic strain induced tyrosine phosphorylation and reorganization of pp125FAK and paxillin and suggest that these focal adhesion proteins play a specific role in cyclic strain-induced morphological change and migration.
Yano
Y
Y
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Geibel
J
J
Sumpio
B E
BE
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000378:metabolism*; D002417:Cattle; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019833:Genistein; D007529:Isoflavones / Q000494:pharmacology; D009570:Nitriles / Q000494:pharmacology; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013314:Stress, Mechanical; D014018:Tissue Distribution; D014443:Tyrosine / Q000378:metabolism*; D020032:Tyrphostins
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D007529:Isoflavones; D009570:Nitriles; D051419:Paxillin; D010750:Phosphoproteins; D020032:Tyrphostins; C079836:tyrphostin 25; D019000:Phosphotyrosine; D014443:Tyrosine; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases