The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases.
The seven-transmembrane-spanning receptors for endothelin and thrombin cause proliferation of airway smooth muscle cells and activation of the extracellular regulated kinase and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases.
复制标题
内皮素和凝血酶的七次跨膜受体导致气道平滑肌细胞增殖，并激活细胞外调节激酶和丝裂原激活蛋白激酶的 c-Jun NH2 末端激酶组。
DOI：
10.1074/jbc.271.10.5750
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Posada,JA
中科院分区：
文献类型：
--
作者：
Shapiro,PS;Evans,JN;Davis,RJ;Posada,JA
在呼吸道平滑肌细胞中，与七个跨膜的内皮素和凝血酶受体结合的配体可刺激细胞生长。丝裂原活化蛋白激酶的胞外调节蛋白2和c-jun氨基末端的激活组也被迅速激活。这些结果证明了一种新的七跨膜受体信号转导机制，涉及Jun激酶通路的激活。受体偶联到Jun激酶的激活可能涉及异三聚体G蛋白，因为在用氟化铝处理的细胞中，该激酶是被酶激活的。免疫复合酶法检测Raf-1活性显示，血小板衍生生长因子和佛波酯均能刺激Raf-1活性，而凝血酶和内皮素对Raf-1无明显刺激作用。这些数据表明，内皮素和凝血酶刺激Raf-1非依赖的丝裂原活化蛋白激酶激活机制。Forsklin激活环磷酸腺苷依赖的蛋白激酶可显著抑制内皮素或凝血酶诱导的丝裂原激活蛋白激酶的激活。用[~3H]胸腺嘧啶核苷掺入DNA的方法测定，Forsklin也显著抑制了气道平滑肌细胞的增殖。
In airway smooth muscle cells ligand binding to the seven-transmembrane endothelin and thrombin receptors stimulates cell growth. Rapid activation of the extracellular regulated kinase 2 and c-Jun NH2-terminal kinase groups of mitogen-activated protein kinases was also observed. The results demonstrate a novel mechanism of seven-transmembrane receptor signaling involving activation of the Jun kinase pathway. Receptor coupling to Jun kinase activation may involve heterotrimeric G proteins since the kinase was enzymatically activated in cells treated with aluminum fluoride. The activity of Raf-1, measured by immune complex kinase assay, revealed that platelet-derived growth factor and phorbol 12-myristate 13-acetate both stimulated Raf-1 activity, while thrombin and endothelin did not appreciably stimulate Raf-1. The data suggest that endothelin and thrombin stimulate Raf-1-independent mechanisms of mitogen-activated protein kinase activation. Endothelin- or thrombin-induced activation of mitogen-activated protein kinases was significantly inhibited by activation of cyclic AMP-dependent protein kinase by forskolin. Proliferation of airway smooth muscle cells, measured by incorporation of [3H]thymidine into DNA, was also greatly attenuated by forskolin.