Stimulation of different subtypes of angiotensin II receptors, AT(1) and AT(2) receptors, regulates STAT activation by negative crosstalk

Angiotensin II type 2 (AT(2)) receptor exerts an inhibitory action on cell growth. In the present study, we report that the Stimulation of AT(2) recep tor in AT(2) receptor cDNA-transfected mt-adult vascular smooth muscle cell s (VSMCs) inhibited angiotensin II type 1 (AT(2)) receptor-mediated tyrosin e phosphorylation of STAT (signal transducers and activators of transcripti on) 1 alpha/beta, STAT2, and STAT3 without influence on Janus kinase. AT(2) receptor activation also inhibited the tyrosine phosphorylation of STAT1 a lpha/beta induced by interferon-gamma, epidermal growth factor, and platele t-derived growth factor. Similar effects of AT(2) receptor were observed in R3T3 fibroblast and mouse fetal VSMCs, which express endogenous AT(2) rece ptor. Moreover, AT(2) receptor inhibited serine:phosphorylation of STAT1 al pha and STAT3 via the inhibition of extracellular signal-regulated kinase ( ERK) activation.: Stimulation of AT(2) receptor inhibited the binding of ST ATs with sis-inducing element in c-fos promoter, resulting:in decreased c-f os expression. Taken together, our results suggest that AT(2) receptor can crosstalk negatively with multiple families of growth receptors by inhibiti ng ERK and STAT activation.