{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,7]],"date-time":"2024-09-07T05:55:23Z","timestamp":1725688523641},"reference-count":49,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2003,8]]},"abstract":"<jats:p> Vascular injury increases nitric oxide (NO) levels, and this effect may play a counterregulatory role in neointima formation, by decreasing vascular smooth muscle cell motility. However, the mechanisms underlying this effect are not well established. We tested the hypothesis that NO decreases cell motility by increasing the activity of a protein tyrosine phosphatase (PTP), PTP-PEST, in cultured rat aortic smooth muscle cells. Two NO donors increased the activity of PTP-PEST. A cGMP analog mimicked the effect of NO, whereas a guanyl cyclase inhibitor blocked it, indicating that elevated cGMP is both necessary and sufficient to induce PTP-PEST activity. Overexpression of wild-type PTP-PEST induced antimotogenesis, whereas expression of dominant negative PTP-PEST blocked the antimotogenic effect of NO, indicating that increased PTP-PEST activity is both sufficient and necessary to explain the effect of NO. Overexpression of PTP-PEST mimicked NO-induced dephosphorylation of adapter protein p130<jats:sup>cas<\/jats:sup>, whereas dominant negative PTP-PEST blocked the effect of NO, indicating that upregulation of PTP-PEST is both necessary and sufficient to explain NO-induced p130<jats:sup>cas<\/jats:sup> dephosphorylation. Expression of a substrate domain-deleted p130<jats:sup>cas<\/jats:sup> decreased motogenesis, whereas overexpression of wild-type p130<jats:sup>cas<\/jats:sup> blocked the antimotogenic effect of NO, indicating the functional importance of p130<jats:sup>cas<\/jats:sup> dephosphorylation. NO induced dissociation of the Cas-Crk complex, an effect that was mimicked by overexpression of PTP-PEST and opposed by expression of dominant negative PTP-PEST. Our results indicate that NO decreases aortic smooth muscle cell motility via a cGMP-mediated mechanism, involving upregulation of PTP-PEST, in turn inducing dephosphorylation of p130<jats:sup>cas<\/jats:sup>, and likely involving Cas-Crk dissociation as a downstream event. <\/jats:p>","DOI":"10.1152\/ajpheart.01127.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:11:15Z","timestamp":1425413475000},"page":"H710-H721","source":"Crossref","is-referenced-by-count":16,"title":["Nitric oxide-induced inhibition of aortic smooth muscle cell motility:  role of PTP-PEST and adaptor proteins p130<sup>cas<\/sup> and Crk"],"prefix":"10.1152","volume":"285","author":[{"given":"Yi","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Physiology and Vascular Biology Center, University of  Tennessee, Memphis, Tennessee 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alice Corina","family":"Ceacareanu","sequence":"additional","affiliation":[{"name":"Department of Physiology and Vascular Biology Center, University of  Tennessee, Memphis, Tennessee 38163"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aviv","family":"Hassid","sequence":"additional","affiliation":[{"name":"Department of Physiology and Vascular Biology Center, University of  Tennessee, Memphis, Tennessee 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