title: Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor.
abstract: 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.
authors.affiliation: Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: M B
authors.initials: MB
authors.lastname: Marrero
authors.forename: B
authors.initials: B
authors.lastname: Schieffer
authors.forename: W G
authors.initials: WG
authors.lastname: Paxton
authors.forename: L
authors.initials: L
authors.lastname: Heerdt
authors.forename: B C
authors.initials: BC
authors.lastname: Berk
authors.forename: P
authors.initials: P
authors.lastname: Delafontaine
authors.forename: K E
authors.initials: KE
authors.lastname: Bernstein
mesh_terms: D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001011:Aorta; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D004815:Epidermal Growth Factor / Q000378:metabolism; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D053614:Janus Kinase 2; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051381:Rats; D011945:Receptors, Angiotensin / Q000378:metabolism*; D050794:STAT1 Transcription Factor; D050795:STAT2 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D011945:Receptors, Angiotensin; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050795:STAT2 Transcription Factor; C494084:STAT2 protein, human; C494081:Stat1 protein, rat; D015534:Trans-Activators; D000804:Angiotensin II; D014443:Tyrosine; D004815:Epidermal Growth Factor; D007371:Interferon-gamma; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507927:Jak2 protein, rat; D053614:Janus Kinase 2