Involvement of rho p21 in cyclic strain-induced tyrosine phosphorylation of focal adhesion kinase (pp125FAK), morphological changes and migration of endothelial cells.
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 botulinum C3 transferase (C3) was used as a specific inhibitor of rho p21. Preincubation of EC with C3 inhibited ADP-ribosylation of rho (94%) and inhibited the morphological change, reorganization of actin filaments, and migration induced by cyclic strain. Moreover, C3 inhibited the cyclic strain-induced tyrosine phosphorylation of pp125FAK and paxillin. These results demonstrate that rho downregulates the tyrosine phosphorylation of pp125FAK and paxillin and can modulate the morphological changes and migration induced by cyclic strain.
Yano
Y
Y
Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06510, USA.
Saito
Y
Y
Narumiya
S
S
Sumpio
B E
BE
D036002:ADP Ribose Transferases / Q000494:pharmacology; D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic; D001905:Botulinum Toxins; 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* / Q000187:drug effects / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000302:isolation & purification / Q000378:metabolism*; D008937:Mitomycins / Q000494:pharmacology; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D019000:Phosphotyrosine; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013314:Stress, Mechanical; D020741:rho GTP-Binding Proteins
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D008937:Mitomycins; D051419:Paxillin; D010750:Phosphoproteins; D000246:Adenosine Diphosphate Ribose; D019000:Phosphotyrosine; D036002:ADP Ribose Transferases; C063007:exoenzyme C3, Clostridium botulinum; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D001905:Botulinum Toxins; D019204:GTP-Binding Proteins; D020741:rho GTP-Binding Proteins