title: Differential regulation of somatostatin receptor dephosphorylation by β-arrestin1 and β-arrestin2.
abstract: Signaling of G protein-coupled receptors (GPCRs) is tightly regulated by coordinated phosphorylation of intracellular serine and threonine residues. Although the mechanisms of agonist-induced phosphorylation have been deciphered for many GPCRs, the regulation of their dephosphorylation remains poorly understood. Using a combination of siRNA knockdown screening and phosphosite-specific antibodies, we have recently identified the catalytic subunit β of protein phosphatase 1 (PP1β) as major constituent of the GPCR phosphatase responsible for dephosphorylation of the sst2 somatostatin receptor. However, PP1-targeting subunits specifically required for GPCR dephosphorylation have not been identified so far. Here, we show that siRNA knockdown of β-arrestin1 strongly inhibits sst2 receptor dephosphorylation. Co-immunoprecipitation experiments demonstrate that β-arrestin1 and PP1β exist as constitutive complex that mediates rapid dephosphorylation of sst2 receptors at or near the plasma membrane. By contrast, β-arrestin2 is not essential for rapid sst2 receptor dephosphorylation. Together, these findings reveal a novel scaffolding function of β-arrestin1 that facilitates efficient targeting of PP1β to phosphorylated GPCRs.
authors.affiliation: Department of Pharmacology and Toxicology, Jena University Hospital, Friedrich Schiller University Jena, Drackendorfer Strasse 1, 07747, Jena, Germany.
authors.forename: Andrea
authors.initials: A
authors.lastname: Kliewer
authors.forename: Stefan
authors.initials: S
authors.lastname: Schulz
mesh_terms: D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D010766:Phosphorylation; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000008:administration & dosage; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D017481:Receptors, Somatostatin; D000071557:beta-Arrestins; D054645:Protein Phosphatase 1