Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor.
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.
Marrero
M B
MB
Department of Pathology, Emory University, Atlanta, Georgia 30322, USA.
Schieffer
B
B
Paxton
W G
WG
Heerdt
L
L
Berk
B C
BC
Delafontaine
P
P
Bernstein
K E
KE
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
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