{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,13]],"date-time":"2024-09-13T04:33:46Z","timestamp":1726202026807},"reference-count":44,"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>Thrombin is involved in abnormal proliferation of vascular smooth muscle cells (VSMCs) associated with pathogenic vascular remodeling. Thrombin stimulation results in extracellular signal-regulated kinase (ERK)1\/2 activation through transactivation of the epidermal growth factor receptor (EGFR). Here, using specific antibodies and inhibitors, we investigated the thrombin-induced phosphorylation of Src family kinases, nonreceptor proline-rich tyrosine kinase (Pyk2), EGFR, and ERK1\/2. Our results show that Src and Pyk2 are involved upstream of the EGFR transactivation that is required for ERK1\/2 phosphorylation. The investigation of the role of intracellular calcium concentration ([Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>) and calcium mobilization with the Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>chelator BAPTA and thapsigargin, respectively, indicated that thrombin- and thapsigargin-induced phosphorylation of the EGFR but not ERK1\/2 is dependent on an increase in [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>. Moreover, only after BAPTA-AM pretreatment was thrombin-induced activation of ERK1\/2 partially preserved from the effects of EGFR and PKC inhibition but not Src family kinase inhibition. These results suggest that BAPTA, by preventing [Ca<jats:sup>2<\/jats:sup><jats:sup>+<\/jats:sup>]<jats:sub>i<\/jats:sub>elevation, unmasks a new pathway of Src family kinase-dependent thrombin-stimulated ERK1\/2 phosphorylation that is independent of EGFR and PKC activation.<\/jats:p>","DOI":"10.1152\/ajpheart.01042.2002","type":"journal-article","created":{"date-parts":[[2015,3,3]],"date-time":"2015-03-03T20:11:15Z","timestamp":1425413475000},"page":"H745-H754","source":"Crossref","is-referenced-by-count":27,"title":["Evidence for ERK1\/2 activation by thrombin that is independent of EGFR transactivation"],"prefix":"10.1152","volume":"285","author":[{"given":"R\u00e9gis","family":"Bobe","sequence":"first","affiliation":[{"name":"Unit\u00e9 Mixte de Recherche 7131, Centre Nationale de la Recherche Scientifique, H\u00f4pital Broussais, 75014 Paris, 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