Cross-talk between angiotensin II receptors and the tyrosine kinases and phosphatases

In addition to its well known involvement in G(q/11)-mediated vasoconstrict ion and its key roles in the homeostasis of electrolyte balances, the angio tensin II type 1 (AT(1)) receptor activates mitogen-activated protein kinas e (MAPK) and p42/44 extracellular signal-regulated kinase. The extracellula r signal regulated kinase activation is mediated by activation of p21-Ras, Raf-1, and MAPK kinase in rat vascular smooth muscle cells. The mechanism f or G(q)-mediated activation of the tyrosine kinase pathways has not been cl ear. It was found that the initial release of intracellular Ca2+ results in the activation of the epidermal growth factor receptor (EGF-R), without au tocrine release of epidermal growth factor. ECF-R provides a scaffold neede d for the activation of p21-Ras, which leads to the activation of MAPK. MAP K plays pivotal roles in the activation of complex growth-promoting pathway s. The pathway from the EGF-R involves protein tyrosine phosphorylation ini tiated by AT(1) receptors. On the other hand, the angiotensin II type 2 (AT (2)) receptor counteracts the AT(1) receptor-mediated tyrosine kinase activ ation by activating several tyrosine phosphatases and serine/threonine phos phatases, and it suppresses the cell growth process stimulated by various g rowth factors. The relative importance of AT(1) and AT(2) receptor actions depends on the levels of AT(1) and AT(2) receptor expression.