title: Ezrin, radixin, and moesin phosphorylation in NIH3T3 cells revealed angiotensin II type 1 receptor cell-type-dependent biased signaling.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, Japan.
authors.forename: Islam A A E-H
authors.initials: IA
authors.lastname: Ibrahim
authors.forename: Michio
authors.initials: M
authors.lastname: Nakaya
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurose
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D019390:Arrestins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction; D000071557:beta-Arrestins; D000099149:Ezrin
chemical_list: D000804:Angiotensin II; D019390:Arrestins; D003598:Cytoskeletal Proteins; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D008565:Membrane Proteins; D008840:Microfilament Proteins; D044140:Receptor, Angiotensin, Type 1; D000071557:beta-Arrestins; D000099149:Ezrin; C071058:moesin; C071776:radixin