Eguchi S, Matsumoto T, Motley E D, Utsunomiya H, Inagami T
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
J Biol Chem. 1996 Jun 14;271(24):14169-75. doi: 10.1074/jbc.271.24.14169.
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.
在培养的大鼠血管平滑肌细胞中，血管紧张素II（Ang II）通过血管紧张素II 1型受体诱导丝裂原活化蛋白激酶（MAPK）活性迅速增加，该受体对百日咳毒素不敏感，但被磷脂酶C抑制剂U73122所阻断。Ang II诱导的MAPK活化不受蛋白激酶C抑制剂GF109203X的影响，仅在用佛波酯预处理时部分受损，而这两种处理均完全阻止了佛波酯诱导的MAPK活化。TMB - 8螯合细胞内Ca2+可消除Ang II诱导的MAPK活化，而细胞外Ca2+螯合或抑制Ca2+内流则无此作用。钙调蛋白抑制剂卡米达唑和酪氨酸激酶抑制剂染料木黄酮可完全阻断Ang II以及Ca2+离子载体A23187诱导的MAPK活化。Ang II导致GTP与p21(ras)的结合迅速增加，这被染料木黄酮、TMB - 8和卡米达唑抑制，但不受百日咳毒素或GF109203X抑制。这些数据表明，Ang II通过血管紧张素II 1型受体诱导的MAPK活化可能由p21(ras)活化介导，该活化通过目前尚未明确的位于Gq偶联的Ca2+/钙调蛋白信号下游的酪氨酸激酶实现。
