DIRECT STIMULATION OF JAK/STAT PATHWAY BY THE ANGIOTENSIN-II AT(1) RECEPTOR

THE peptide angiotensin II is the effector molecule of the renin-angiotensin 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 AT(1) (refs 1, 2). These receptors contain the structural features of the G-protein-coupled receptor superfamily(3). 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 increase 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 AT(1) receptor, indicating that G-protein-coupled receptors may be able to signal through the intracellular phosphorylation pathways used by cytokine receptors(4,5).