Endothelial nitric oxide synthase gene transfer inhibits platelet-derived growth factor-BB stimulated focal adhesion kinase and paxillin phosphorylation in vascular smooth muscle cells.
Stimulation of smooth muscle (VSM) cells of guinea pig coronary artery by platelet-derived growth factor (PDGF)-BB retards paxillin mobility (mobility shift) in SDS-PAGE in a time-dependent manner. This mobility shift may be due to tyrosine phosphorylation of paxillin. eNOS gene transfer by replication deficient recombinant adenovirus vector AD5/RSVeNOS in VSM cells inhibited PDGF-BB-stimulated mobility shift and tyrosine phosphorylation of paxillin. Concomitantly, tyrosine phosphorylation of focal adhesion kinase (FAK) was also inhibited. The inhibition of paxillin and FAK tyrosine phosphorylation did not affect stress fiber and focal adhesion formation. Considering the importance of FAK and paxillin in cell migration and proliferation, these results suggest that the FAK-paxillin pathway is a target for NO action to inhibit VSM cell migration and proliferation.
Fang
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University of Iowa College of Medicine Department of Anatomy and Cell Biology, Iowa City 52242, USA.
Sharma
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Bhalla
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D000818:Animals; D000077214:Becaplermin; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002455:Cell Division; D002465:Cell Movement; D003331:Coronary Vessels; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology*; D051416:Focal Adhesion Protein-Tyrosine Kinases; D018014:Gene Transfer Techniques; D006168:Guinea Pigs; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000648:ultrastructure; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000502:physiology*; D051419:Paxillin; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis
D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D051419:Paxillin; D010750:Phosphoproteins; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D000077214:Becaplermin; D019000:Phosphotyrosine; D019001:Nitric Oxide Synthase; D011505:Protein-Tyrosine Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases