Angiotensin II induced rapid MAPK activation in cultured rat vascular smooth muscle cells via the Ang II type 1 receptor, mediated by p21(ras) activation and a downstream tyrosine kinase.
Demonstrates that Angiotensin II activates MAPK in vascular smooth muscle cells via a Ca2+/calmodulin and tyrosine kinase-dependent p21(ras) pathway.
In cultured rat vascular smooth muscle cells, angiotensin II (Ang II) induced a rapid increase in mitogen-activated protein kinase (MAPK) activity through the Ang II type 1 receptor, which was insensitive to pertussis toxin but was abolished by the phospholipase C inhibitor, U73122. The Ang II-induced MAPK activation was not affected by the protein kinase C inhibitor, GF109203X, and was only partially impaired by pretreatment with a phorbol ester, whereas both treatments completely prevented MAPK activation by the phorbol ester. Intracellular Ca2+ chelation by TMB-8, but not extracellular Ca2+ chelation or inhibition of Ca2+ influx, abolished Ang II-induced MAPK activation. The calmodulin inhibitor, calmidazolium, and the tyrosine kinase inhibitor, genistein, completely blocked MAPK activation by Ang II as well as by the Ca2+ ionophore A23187. Ang II caused a rapid increase in the binding of GTP to p21(ras), and this was inhibited by genistein, TMB-8, and calmidazolium but not by pertussis toxin or GF109203X. These data suggest that Ang II-induced MAPK activation through the Ang II type 1 receptor could be mediated by p21(ras)activation through a currently unidentified tyrosine kinase that lies downstream of Gq-coupled Ca2+/calmodulin signals.
Eguchi et al. (1996) studied this question. Angiotensin II was evaluated on Mitogen-activated protein kinase (MAPK) activity and p21(ras) activation. Angiotensin II induced rapid MAPK activation in cultured rat vascular smooth muscle cells via the Ang II type 1 receptor, mediated by p21(ras) activation and a downstream tyrosine kinase.