Angiotensin II stimulates rapid serine phosphorylation of transcription factor Stat3

Mol Cell Biochem. 1997 May;170(1-2):171-6. doi: 10.1023/a:1006865721939.


In rat neonatal cardiac fibroblasts and CHO-K1 cells expressing angiotensin type 1 receptors, angiotensin II (AII) rapidly caused a time dependent reduction in the SDS-polyacrylamide gel electrophoretic mobility of Stat3 (Signal Transducer and Activator of Transcription). This was concentration dependent and detected at a low/physiological concentration of AII (1 nM), with initial effect observed as early as 2 min; and maximal at 5 min. The rapid stimulation of Stat3 mobility retardation by AII, paralleled the rapid activation of MAP kinases (mitogen-activated protein kinases), and both were sensitive to the MAP kinase kinase 1 inhibitor, PD98059. Immunoprecipitation of Stat3 from [32P] labeled cells demonstrated a 4-fold increase in Stat3 phosphorylation in response to AII, and phosphoamino acid analysis indicated that phosphorylation occurred on serine residues. Angiotensin II-induced rapid phosphorylation of Stat3 was also sensitive to the MAP kinase kinase 1 inhibitor, PD98059. Treatment of immunoprecipitated Stat3 from AII-treated cells with protein phosphatase- PP-2A, reversed the AII-induced retardation of Stat3 mobility. These results demonstrate that AII rapidly induces Stat3 serine phosphorylation through a MAP kinase kinase 1 dependent pathway. Rapid stimulation of Stat3 serine phosphorylation by AII may have implications in the modulation of its transcriptional activity and gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin I
  • Angiotensin II / pharmacology*
  • Animals
  • Animals, Newborn
  • CHO Cells
  • Cricetinae
  • DNA-Binding Proteins / isolation & purification
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Fibroblasts / metabolism
  • Flavonoids / pharmacology
  • Kinetics
  • Mitogen-Activated Protein Kinase Kinases
  • Myocardium / metabolism*
  • Phosphoprotein Phosphatases
  • Phosphorylation
  • Protein Kinase Inhibitors
  • Rats
  • Receptors, Angiotensin / biosynthesis
  • Receptors, Angiotensin / physiology*
  • Recombinant Proteins / metabolism
  • STAT3 Transcription Factor
  • Serine
  • Trans-Activators / isolation & purification
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism*
  • Transfection


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • Flavonoids
  • Protein Kinase Inhibitors
  • Receptors, Angiotensin
  • Recombinant Proteins
  • STAT3 Transcription Factor
  • Stat3 protein, rat
  • Trans-Activators
  • Transcription Factors
  • Angiotensin II
  • Serine
  • Angiotensin I
  • Mitogen-Activated Protein Kinase Kinases
  • Phosphoprotein Phosphatases
  • 2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one