Angiotensin II mediated signal transduction - Important role of tyrosine kinases

It has been 100 years since the discovery of renin by Bergman and Tigersted t. Since then, numerous studies have advanced our understanding of the reni n-angiotensin system. A remarkable aspect was the discovery that angiotensi n II (AngII) is the central product of the renin-angiotensin system and tha t this octapeptide induces multiple physiological responses in different ce ll types. In addition to its well known vasoconstrictive effects, growing e vidence supports the notion that AngII may play a central role not only in hypertension, but also in cardiovascular and renal diseases. Binding of Ang II to the seven-transmembrane angiotensin II type 1 receptor is responsible for nearly all of the physiological actions of AngII. Recent studies under score the new concept that activation of intracellular second messengers by AngII requires tyrosine phosphorylation. An increasing number of tyrosine kinases have been shown to be activated by AngII, including the Src kinase family, the focal adhesion kinase family, the Janus kinases and receptor ty rosine kinases. These actions of AngII contribute to the pathophysiology of cardiac hypertrophy and remodeling, vascular thickening, heart failure and atherosclerosis. In this review, we discuss the important role of tyrosine kinases in AngII-mediated signal transduction. Understanding the importanc e of tyrosine phosphorylation in AngII-stimulated signaling events may cont ribute to new therapies for cardiovascular and renal diseases. (C) 2000 Els evier Science B.V. All rights reserved.