Thrombospondin-1-induced migration is functionally dependent upon focal adhesion kinase.
Vascular smooth muscle cell migration is important in vascular disease. Previously, we showed thrombospondin-1 activates focal adhesion kinase in these cells. We hypothesized that focal adhesion kinase is important for thrombspondin-1-induced vascular smooth muscle cell migration. Bovine aortic smooth muscle cells were transfected with FAK397, FAK-wild type, pcDNA, or beta-Gal plasmids. Migration was assessed with thrombospondin-1 or serum-free medium in quiescent transfected cells or quiescent cells pretreated with the focal adhesion kinase inhibitor, geldanamycin. Number of cells migrated per 5 fields (x400) were recorded. Antihemagglutinin immunoprecipitation and Western blot were used to examine thrombospondin-1-induced focal adhesion kinase phosphorylation in transfected cells. FAK397 transfection inhibited thrombospondin-1-induced focal adhesion kinase phosphorylation and migration (P < .05). Geldanamycin inhibited thrombospondin-1-induced smooth muscle cell migration (P < .05). In conclusion, vascular smooth muscle cells transfected with FAK397 inhibited thrombosponin-1-induced migration and tyrosine phosphorylation. Further, geldanamycin also inhibited migration. These results suggest focal adhesion kinase is involved in thrombospondin-1-induced vascular smooth muscle cell migration.
Wang
Xiu-Jie
XJ
Section of Vascular Surgery, Yale University School of Medicine, New Haven, CT, USA.
Maier
Kristopher
K
Fuse
Shoichi
S
Willis
Alliric I
AI
Olson
Eric
E
Nesselroth
Susan
S
Sumpio
Bauer E
BE
Gahtan
Vivian
V
D000818:Animals; D001011:Aorta / Q000201:enzymology; D016227:Benzoquinones / Q000494:pharmacology; D002417:Cattle; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology*; D009154:Mutation; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D019700:Thrombospondin 1 / Q000378:metabolism*; D014162:Transfection
D016227:Benzoquinones; D047029:Lactams, Macrocyclic; D047428:Protein Kinase Inhibitors; D019700:Thrombospondin 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C001277:geldanamycin