Signal transduction of angiotensin II type 1 receptor through receptor tyrosine kinase

In cultured vascular smooth muscle cells, the angiotensin II (AngII) type-1 (AT(1)) receptor generates growth-promoting signals via the epidermal grow th factor (EGF) receptor system. This 'transactivation' mechanism now appea rs to be utilized by a variety of G-protein-coupled receptors in many cells . The AngII-induced EGF receptor transactivation leads to activation of dow nstream signaling molecules including Ras, ERK, c-fos, Akt/protein kinase B , and p70 S6 kinase. We propose three possible mechanisms may be involved i n the transactivation, (i) an upstream tyrosine kinase, (ii) reactive oxyge n species, and (iii) a juxtacrine activation of the EGF receptor ligand. Wh ether the EGF receptor signal transduction induced by AngII plays an essent ial role in cardiovascular remodeling remains to be investigated. (C) 2000 Elsevier Science B.V. All rights reserved.