{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T03:29:43Z","timestamp":1773286183498,"version":"3.50.1"},"reference-count":47,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:p> We analyzed the signaling pathways initiated by endothelin receptors ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B<\/jats:sub> in intestinal circular and longitudinal smooth muscle cells. The response to endothelin-1 (ET-1) consisted of two phases in both cell types. The initial, transient phase of contraction and phosphorylation of 20-kDa myosin light chain (MLC<jats:sub>20<\/jats:sub>) was mediated additively by ET<jats:sub>A<\/jats:sub> and ET<jats:sub>B<\/jats:sub> receptors and initiated by G\u03b1<jats:sub>q<\/jats:sub>-, Ca<jats:sup>2+<\/jats:sup>\/calmodulin-dependent activation of MLC kinase. In contrast, the sustained phase was mediated selectively by ET<jats:sub>A<\/jats:sub> receptors via a pathway involving sequential activation of G\u03b1<jats:sub>13<\/jats:sub>, RhoA, and Rho kinase, resulting in phosphorylation of MYPT1 at Thr<jats:sup>696<\/jats:sup> and phosphorylation of MLC<jats:sub>20<\/jats:sub>. Although PKC was activated, CPI-17 was not phosphorylated and hence did not contribute to inhibition of MLC phosphatase. The absence of CPI-17 phosphorylation by PKC reflected active dephosphorylation of CPI-17 by protein phosphatase 2A (PP2A). PP2A was activated via a pathway involving ET<jats:sub>B<\/jats:sub>-dependent stimulation of p38 MAPK activity. CPI-17 phosphorylation was unmasked in the presence of the ET<jats:sub>B<\/jats:sub> antagonist BQ-788, but not the ET<jats:sub>A<\/jats:sub> antagonist BQ-123, and in the presence of a low concentration of okadaic acid, which selectively inactivates PP2A. The resultant phosphorylation of CPI-17 was blocked by bisindolylmaleimide, providing direct confirmation that it was PKC dependent. We conclude that the two phases of the intestinal smooth muscle response to ET-1 involve distinct receptors, G proteins, and signaling pathways. The sustained response is mediated via selective ET<jats:sub>A<\/jats:sub>-dependent phosphorylation of MYPT1. In contrast, ET<jats:sub>B<\/jats:sub> initiates an inhibitory pathway involving p38 MAPK-dependent activation of PP2A that causes dephosphorylation of CPI-17. <\/jats:p>","DOI":"10.1152\/ajpcell.00198.2004","type":"journal-article","created":{"date-parts":[[2004,10,9]],"date-time":"2004-10-09T02:38:03Z","timestamp":1097289483000},"page":"C1209-C1218","source":"Crossref","is-referenced-by-count":64,"title":["G<sub>q<\/sub>\/G<sub>13<\/sub> signaling by ET-1 in smooth muscle: MYPT1 phosphorylation via ET<sub>A<\/sub> and CPI-17 dephosphorylation via ET<sub>B<\/sub>"],"prefix":"10.1152","volume":"287","author":[{"given":"Eric","family":"Hersch","sequence":"first","affiliation":[]},{"given":"Jiean","family":"Huang","sequence":"additional","affiliation":[]},{"given":"John R.","family":"Grider","sequence":"additional","affiliation":[]},{"given":"Karnam S.","family":"Murthy","sequence":"additional","affiliation":[]}],"member":"24","reference":[{"key":"R1","unstructured":"Abdel-Latif AA, Yousufzai SY, el-Mowafy AM, and Ye Z. 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