Activation of extracellular signal-activated kinase by angiotensin II-induced Gq-independent epidermal growth factor receptor transactivation

Hypertens Res. 2004 Oct;27(10):765-70. doi: 10.1291/hypres.27.765.


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.

MeSH terms

  • Angiotensin II / analogs & derivatives*
  • Angiotensin II / pharmacology*
  • Animals
  • Arteries
  • CHO Cells
  • Cells, Cultured
  • Coronary Vessels / cytology
  • Coronary Vessels / metabolism
  • Cricetinae
  • Cricetulus
  • Enzyme Activation / physiology
  • ErbB Receptors / genetics*
  • Extracellular Signal-Regulated MAP Kinases / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / physiology*
  • Green Fluorescent Proteins / genetics
  • Humans
  • Inositol Phosphates / biosynthesis
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / metabolism
  • Receptor, Angiotensin, Type 1 / genetics
  • Recombinant Fusion Proteins / metabolism
  • Transcriptional Activation / physiology*


  • Inositol Phosphates
  • Receptor, Angiotensin, Type 1
  • Recombinant Fusion Proteins
  • angiotensin II, Sar(1)-Ile(4)-Ile(8)-
  • enhanced green fluorescent protein
  • Angiotensin II
  • Green Fluorescent Proteins
  • ErbB Receptors
  • Extracellular Signal-Regulated MAP Kinases
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • GTP-Binding Protein alpha Subunits, Gq-G11