Angiotensin II plays a critical role in the regulation of vascular resistance and intravascular volume. Virtually all of the physiologic effects of angiotensin II are mediated by the AT(1) receptor, a seven-transmembrane spanning receptor. Although G proteins play an important role in the signaling of this class of receptors, it has become increasingly clear that tyrosine phosphorylation is also intimately involved in AT(1) receptor signaling. In response to angiotensin II, both smooth muscle and glomerular mesangial cells tyrosine phosphorylate the γ isoform of phospholipase C. This is critical to downstream signaling events, including the intracellular generation of 1,4,5-inositol triphosphate. The soluble cytoplasmic kinase Src appears to be activated by angiotensin II and to play an important role in the phosphorylation of phospholipase C. Angiotensin II, acting through the AT(1) receptor, causes Jak kinase phosphorylation and activation. This, in turn, leads to STAT phosphorylation and translocation to the nucleus. Finally, we present data that indicate that angiotensin II activates Ras and leads to Ras-Raf-1 complex formation. Activation of this pathway also appears to require active Src. These studies provide compelling evidence that tyrosine phosphorylation plays an important role in the signaling of angiotensin II. The exact biochemical mechanism by which a seven-transmembrane receptor stimulates intracellular kinases to be elucidated. (Trends Cardiovasc Med 1996;6:179-187).
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