Involvement of rho p21 in Cyclic Strain-Induced Tyrosine Phosphorylation of Focal Adhesion Kinase (pp125FAK), Morphological Changes and Migration of Endothelial Cells

• Published in: Biochemical and biophysical research communications 1996-07, Vol.224 (2), p.508-515
• Main Authors: Yano, Yoshiko, Saito, Yuji, Narumiya, Shuh, Sumpio, Bauer E.
• Format: Article
• Language: English
• Subjects: Adenosine Diphosphate Ribose - metabolism; ADP Ribose Transferases - pharmacology; Animals; Aorta, Thoracic; Botulinum Toxins; Cattle; Cell Adhesion Molecules - metabolism; Cell Movement - drug effects; Cells, Cultured; Cytoskeletal Proteins - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiology; Focal Adhesion Kinase 1; Focal Adhesion Protein-Tyrosine Kinases; GTP-Binding Proteins - antagonists & inhibitors; GTP-Binding Proteins - isolation & purification; GTP-Binding Proteins - metabolism; Mitomycins - pharmacology; Paxillin; Phosphoproteins - metabolism; Phosphorylation; Phosphotyrosine; Protein-Tyrosine Kinases - metabolism; rho GTP-Binding Proteins; Stress, Mechanical
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1996.1057

The molecular mechanisms by which endothelial cells sense and respond to physical forces remain to be elucidated. Recently we reported that cyclic strain-induced morphological change and migration of EC were regulated by the tyrosine phosphorylation of focal adhesion kinase (pp125FAK) and paxillin. The aim of the present study was to clarify the role of the small GTP-binding protein rho p21 in EC exposed to cyclic strain. Bovine aortic endothelial cells (EC) were subjected to 10% average strain at 60 cycle/min.Clostridium botulinumC3transferase (C3) was used as a specific inhibitor of rho p21. Preincubation of EC with C3inhibited ADP-ribosylation of rho (94%) and inhibited the morphological change, reorganization of actin filaments, and migration induced by cyclic strain. Moreover, C3inhibited the cyclic strain-induced tyrosine phosphorylation of pp125FAKand paxillin. These results demonstrate that rho downregulates the tyrosine phosphorylation of pp125FAKand paxillin and can modulate the morphological changes and migration induced by cyclic strain.