Activation of extracellular signal-activated kinase by angiotensin II-induced Gq-independent epidermal growth factor receptor transactivation.
Multiple signaling pathways link the angiotensin II (Ang II) type 1 (AT1) 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, [Sar1, Ile4, Ile8]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 AT1. This activation was mostly mediated by [Sar1, Ile4, Ile8]Ang II-induced Gq-independent epidermal growth factor receptor transactivation. We found that AT1 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.
Miura
Shin-ichiro
S
Department of Cardiology, Fukuoka University School of Medicine, Fukuoka, Japan. miuras@cis.fukuoka-u.ac.jp
Zhang
Jingli
J
Matsuo
Yoshino
Y
Saku
Keijiro
K
Karnik
Sadashiva S
SS
D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D001158:Arteries; D016466:CHO Cells; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation / Q000502:physiology; D066246:ErbB Receptors / Q000235:genetics*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D007295:Inositol Phosphates / Q000096:biosynthesis; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015533:Transcriptional Activation / Q000502:physiology*
D007295:Inositol Phosphates; D044140:Receptor, Angiotensin, Type 1; D011993:Recombinant Fusion Proteins; C502020:angiotensin II, Sar(1)-Ile(4)-Ile(8)-; C485184:enhanced green fluorescent protein; D000804:Angiotensin II; D049452:Green Fluorescent Proteins; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D043802:GTP-Binding Protein alpha Subunits, Gq-G11