Role of PTP-1B in aortic smooth muscle cell motility and tyrosine phosphorylation of focal adhesion proteins.
Recent studies have focused attention on the role of protein tyrosine kinases in vascular smooth muscle cell biology, but similar information regarding protein tyrosine phosphatases (PTP) is sparse. PTP-1B is a ubiquitous nonreceptor phosphatase with uncertain function and substrates that are mostly unidentified. We used antisense oligodeoxynucleotides (ODN) against PTP-1B to investigate the role of endogenous PTP-1B in motility of primary cultures of rat aortic smooth muscle cells (RASMC). Antisense ODN decreased PTP-1B protein levels and activity in a concentration-dependent fashion, whereas sense, scrambled, or three-base mismatch antisense ODN had little or no effect. Treatment of cells with antisense ODN, but not sense, scrambled, or three-base mismatch antisense ODN, enhanced cell motility and increased tyrosine phosphorylation levels of focal adhesion proteins paxillin, p130(cas), and focal adhesion kinase. Our findings indicate that PTP-1B is a negative regulator of RASMC motility via modulation of phosphotyrosine levels in several focal adhesion proteins and suggest the involvement of PTP-1B in events such as atherosclerosis and restenosis, which are associated with increased vascular smooth muscle cell motility.
Department of Physiology, University of Tennessee, Memphis, Tennessee 38163, USA. ahassid@physio1.utmem.edu
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D000818:Animals; D001011:Aorta / Q000166:cytology*; D002352:Carrier Proteins / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D008565:Membrane Proteins / Q000502:physiology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D020319:Oligodeoxyribonucleotides, Antisense; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; D011505:Protein-Tyrosine Kinases / Q000378:metabolism* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018909:src Homology Domains
D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; D008565:Membrane Proteins; D020319:Oligodeoxyribonucleotides, Antisense; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D017027:Protein Tyrosine Phosphatases; C516610:Ptpn1 protein, rat