Activation of extracellular signal-activated kinase by angiotensin II-induced Gq-independent epidermal growth factor receptor transactivation
Activation of extracellular signal-activated kinase by angiotensin II-induced Gq-independent epidermal growth factor receptor transactivation
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DOI：
10.1291/hypres.27.765
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发表时间：
2004-10-01
影响因子：
5.4
通讯作者：
Karnik, SS
中科院分区：
文献类型：
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作者：
Miura, S;Zhang, JL;Karnik, SS
多种信号通路将血管紧张素 II (Ang II) 1 型 (AT(1)) 受体与 Gq 依赖性磷酸肌醇 (IP) 的产生以及 Ang 11 激活的不依赖 Gq 的磷酸细胞外信号激活激酶 (p-ERK) 1/2 联系起来，分别调节心血管血管收缩和细胞生长。 Ang II 类似物 [Sar(1), IIe(4), IIe(8)]Ang II 不会刺激 Gq 依赖性 IP 产生，但仍然在人冠状动脉平滑肌细胞以及稳定表达 AT(1) 的细胞系中激活 Gq 依赖性 p-ERK1/2。这种激活主要是由 [Sar(1), IIe(4), IIe(8)]Ang II 诱导的不依赖于 Gq 的表皮生长因子受体反式激活介导的。我们发现 AT(1) 受体信号传导显示出分叉成功能上独立的途径。清楚地了解这种独特的信号传导对于开发治疗高血压和心脏肥大等疾病的治疗药物可能是必要的。
Multiple signaling pathways link the angiotensin II (Ang II) type 1 (AT(1)) receptor to Gq-dependent inositol phosphate (IP) production and Gq-independent phospho-extracellular signal-activated kinase (p-ERK) 1/2 activation by Ang 11 in the regulation of cardiovascular vasoconstriction and cell growth, respectively. An Ang II analogue, [Sar(1), IIe(4), IIe(8)]Ang II, did not stimulate Gq-dependent IP production, but still activated Gq-independent p-ERK1/2 in human coronary artery smooth muscle cells as well as in a cell line that stably expressed AT(1). This activation was mostly mediated by [Sar(1), IIe(4), IIe(8)]Ang II-induced Gq-independent epidermal growth factor receptor transactivation. We found that AT(1) receptor signaling shows bifurcation into functionally separate pathways. A clear understanding of this unique signaling may be necessary for the development of therapeutic agents to treat disorders such as hypertension and cardiac hypertrophy.