Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor

Nature. 1995 May 18;375(6528):247-50. doi: 10.1038/375247a0.


The peptide angiotensin II is the effector molecule of the reninangiotensin system. All the haemodynamic effects of angiotensin II, including vasoconstriction and adrenal aldosterone release, are mediated through a single class of cell-surface receptors known as AT1 (refs 1, 2). These receptors contain the structural features of the G-protein-coupled receptor superfamily. We show here that angiotensin II induces the rapid phosphorylation of tyrosine in the intracellular kinases Jak2 and Tyk2 in rat aortic smooth-muscle cells and that this phosphorylation is associated with increased activity of Jak2. The Jak family substrates STAT1 and STAT2 (for signal transducers and activators of transcription) are rapidly tyrosine-phosphorylated in response to angiotensin II. We also find that Jak2 co-precipitates with the AT1 receptor, indicating that G-protein-coupled receptors may be able to signal through the intracellular phosphorylation pathways used by cytokine receptors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Angiotensin II / metabolism*
  • Animals
  • Aorta
  • Cell Line
  • DNA-Binding Proteins / metabolism*
  • Enzyme Activation
  • Epidermal Growth Factor / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Janus Kinase 2
  • Muscle, Smooth, Vascular / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Proto-Oncogene Proteins*
  • Rats
  • Receptors, Angiotensin / metabolism*
  • STAT1 Transcription Factor
  • STAT2 Transcription Factor
  • Trans-Activators / metabolism*
  • Tyrosine / metabolism


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Receptors, Angiotensin
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STAT2 Transcription Factor
  • STAT2 protein, human
  • Stat1 protein, rat
  • Trans-Activators
  • Angiotensin II
  • Tyrosine
  • Epidermal Growth Factor
  • Interferon-gamma
  • Protein-Tyrosine Kinases
  • JAK2 protein, human
  • Jak2 protein, rat
  • Janus Kinase 2