期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：19
页码：10782-10787
DOI：10.1073/pnas.1834556100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Stimulation of a mutant angiotensin type 1A receptor (DRY/AAY) with angiotensin II (Ang II) or of a wild-type receptor with an Ang II analog ([sarcosine1,Ile4,Ile8]Ang II) fails to activate classical heterotrimeric G protein signaling but does lead to recruitment of {beta}-arrestin 2-GFP and activation of extracellular signal-regulated kinases 1 and 2 (ERK1/2) (maximum stimulation {approx}50% of wild type). This G protein-independent activation of mitogen-activated protein kinase is abolished by depletion of cellular {beta}-arrestin 2 but is unaffected by the PKC inhibitor Ro-31-8425. In parallel, stimulation of the wild-type angiotensin type 1A receptor with Ang II robustly stimulates ERK1/2 activation with {approx}60% of the response blocked by the PKC inhibitor (G protein dependent) and the rest of the response blocked by depletion of cellular {beta}-arrestin 2 by small interfering RNA ({beta}-arrestin dependent). These findings imply the existence of independent G protein- and {beta}-arrestin 2-mediated pathways leading to ERK1/2 activation and the existence of distinct "active" conformations of a seven-membrane-spanning receptor coupled to each.
