title: Beta-arrestin2 as a competitor for GRK2 interaction with the GLP-1 receptor upon receptor activation.
abstract: The signaling of seven transmembrane receptors/G-protein- coupled receptors (GPCRs) is regulated by a number of receptor interacting proteins, including βarrestins (βarrs) and GPCR kinases (GRKs). In the present report, we have analyzed the interaction pattern between the glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), βarr2, and GRK2 using bioluminescence resonance energy transfer assays. We found that βarr2 interacts with the GLP-1R in a biphasic manner with a phosphorylation-independent and a phosphorylation-dependent component. In competition experiments, we observed βarr2 competing with GRK2 for interaction with GLP-1R. We propose a model were βarr2 competes with GRK2 for interaction with the activated and GRK phosphorylated GLP-1R, suggesting a new role of βarr2 in regulating the orchestration of GRK2 functionality.
authors.affiliation: Hagedorn Research Institute, Måløv, Denmark. rsjr@novonordisk.com
authors.forename: Rasmus
authors.initials: R
authors.lastname: Jorgensen
authors.forename: Sarah
authors.initials: S
authors.lastname: Norklit Roed
authors.forename: Anders
authors.initials: A
authors.lastname: Heding
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elling
mesh_terms: D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D001667:Binding, Competitive; D018076:DNA, Complementary / Q000378:metabolism; D004735:Energy Transfer; D054769:G-Protein-Coupled Receptor Kinase 2 / Q000235:genetics / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D049410:Luciferases, Renilla / Q000235:genetics / Q000378:metabolism; D008163:Luminescent Measurements; D010766:Phosphorylation; D018027:Receptors, Glucagon / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D000071557:beta-Arrestins
chemical_list: D019390:Arrestins; D018076:DNA, Complementary; C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D011993:Recombinant Fusion Proteins; D000071557:beta-Arrestins; D049452:Green Fluorescent Proteins; D049410:Luciferases, Renilla; C496567:GRK2 protein, human; D054769:G-Protein-Coupled Receptor Kinase 2