| First Author | Yuan Z | Year | 2010 |
| Journal | Mol Cell Endocrinol | Volume | 325 |
| Issue | 1-2 | Pages | 1-7 |
| PubMed ID | 20416357 | Mgi Jnum | J:163200 |
| Mgi Id | MGI:4821229 | Doi | 10.1016/j.mce.2010.04.013 |
| Citation | Yuan Z, et al. (2010) Activation of Src protein tyrosine kinase plays an essential role in urocortin-mediated cardioprotection. Mol Cell Endocrinol 325(1-2):1-7 |
| abstractText | Urocortin is a 40 amino acid peptide of the corticotrophin-releasing factor (CRF) family that is synthesized and released by cardiac myocytes. Endogenous urocortin expression is increased during ischemia/reperfusion (I/R) and addition of exogenous urocortin reduces cell death caused by I/R injury. Studies have also showed that the protective action of urocortin is mediated by the activation of ERK1/2. We discovered that a non-receptor tyrosine kinase, Src, is involved in the urocortin-induced activation of ERK1/2 in mouse atrial HL-1 myocytes. The selective Src family kinase inhibitor, PP2, reduced the urocortin-induced phosphorylation of ERK1/2, and so did the expression of a dominant-negative mutant of Src in transfected HL-1 cells. Inhibition of Src by PP2 also reduced urocortin's protective effects in HL-1 cells after hypoxia/reoxygenation (H/R), as assessed by flow cytometry and caspase-3 activation assay. Titration studies indicated that as little as 10(-8)M urocortin was sufficient to induce Src activation. Maximal phosphorylation/activation of Src and ERK1/2 were both detected after 5 min incubation with urocortin. These effects of urocortin were largely mediated by CRF receptor-1, although a minor contribution of CRF receptor-2 cannot be excluded. Here we report for the first time that short-term treatment with urocortin causes rapid phosphorylation of Src, and that the urocortin-activated Src kinase serves as an upstream modulator of ERK1/2 activation, playing an essential role in urocortin-mediated cardioprotection. |
