Ezrin,radixin,and moesin phosphorylation in NIH3T3 cells revealed angiotensin II type 1 receptor cell-type-dependent biased signaling

Β-arrestin-biased agonists are a new class of drugs with promising therapeutic effects. the molecular mechanisms of β-arrestin-biased agonists are still not completely identified. here,we investigated the effect of angiotensin ii (angii) and [sar1,ile4,ile8] angii (sii),a β-arrestin- biased agonist,on ezrin-radixin-moesin (erm) phosphorylation in nih3t3 cells (a fibroblast cell line) stably expressing angii type 1a receptor. erm proteins are cross-linkers between the plasma membrane and the actin cytoskeleton and control a number of signaling pathways. we also investigated the role of gαq protein and β-arrestins in mediating erm phosphorylation. we found that angii stimulates erm phosphorylation by acting as a β-arrestin-biased agonist and angii-stimulated erm phosphorylation is mediated by β-arrestin2 not β-arrestin1. we also found that sii inhibits erm phosphorylation by acting as a gαq protein-biased agonist. we concluded that erm phosphorylation is a unique β-arrestin-biased agonism signal. both angii and sii can activate either gαq protein or β-arrestin-mediated signaling as functional biased agonists according to the type of the cell on which they act. © the japanese pharmacological society.