Stimulation of the AT2 receptor inhibited AT1 receptor-mediated tyrosine phosphorylation of STATs and ERK activation in vascular smooth muscle cells and fibroblasts.
Does AT2 receptor stimulation inhibit AT1 receptor-mediated STAT activation in vascular smooth muscle cells?
AT2 receptor stimulation negatively crosstalks with multiple growth receptors by inhibiting ERK and STAT activation, providing a molecular mechanism for its inhibitory action on cell growth.
Angiotensin II type 2 (AT2) receptor exerts an inhibitory action on cell growth. In the present study, we report that the stimulation of AT2 receptor in AT2 receptor cDNA-transfected rat adult vascular smooth muscle cells (VSMCs) inhibited angiotensin II type 1 (AT1) receptor-mediated tyrosine phosphorylation of STAT (signal transducers and activators of transcription) 1alpha/beta, STAT2, and STAT3 without influence on Janus kinase. AT2 receptor activation also inhibited the tyrosine phosphorylation of STAT1alpha/beta induced by interferon-gamma, epidermal growth factor, and platelet-derived growth factor. Similar effects of AT2 receptor were observed in R3T3 fibroblast and mouse fetal VSMCs, which express endogenous AT2 receptor. Moreover, AT2 receptor inhibited serine phosphorylation of STAT1alpha and STAT3 via the inhibition of extracellular signal-regulated kinase (ERK) activation. Stimulation of AT2 receptor inhibited the binding of STATs with sis-inducing element in c-fos promoter, resulting in decreased c-fos expression. Taken together, our results suggest that AT2 receptor can crosstalk negatively with multiple families of growth receptors by inhibiting ERK and STAT activation.
Horiuchi et al. (Fri,) reported a other. AT2 receptor stimulation was evaluated on STAT and ERK activation. Stimulation of the AT2 receptor inhibited AT1 receptor-mediated tyrosine phosphorylation of STATs and ERK activation in vascular smooth muscle cells and fibroblasts.