Activation of Extracellular Signal-Activated Kinase by Angiotensin II-Induced Gq-Independent Epidermal Growth Factor Receptor Transactivation
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<B>Multiple signaling pathways link the angiotensin II (Ang II) type 1 (AT<SUB>1</SUB>) receptor to Gq-dependent inositol phosphate (IP) production and Gq-independent phospho-extracellular signal-activated kinase (p-ERK) 1/2 activation by Ang II in the regulation of cardiovascular vasoconstriction and cell growth, respectively. An Ang II analogue, [Sar<SUP>1</SUP>, Ile<SUP>4</SUP>, Ile<SUP>8</SUP>]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<SUB>1</SUB>. This activation was mostly mediated by [Sar<SUP>1</SUP>, Ile<SUP>4</SUP>, Ile<SUP>8</SUP>]Ang II-induced Gq-independent epidermal growth factor receptor transactivation. We found that AT<SUB>1</SUB> 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. (<I>Hypertens Res</I> 2004; 27: 765-770)</B>
- 日本高血圧学会の論文
日本高血圧学会 | 論文
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