Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization.
beta-Arrestins are proteins that bind phosphorylated heterotrimeric GTP-binding protein (G protein)-coupled receptors (GPCRs) and contribute to the desensitization of GPCRs by uncoupling the signal transduction process. Resensitization of GPCR responsiveness involves agonist-mediated receptor sequestration. Overexpression of beta-arrestins in human embryonic kidney cells rescued the sequestration of beta 2-adrenergic receptor (beta 2AR) mutants defective in their ability to sequester, an effect enhanced by simultaneous overexpression of beta-adrenergic receptor kinase 1. Wild-type beta 2AR sequestration was inhibited by the overexpression of two beta-arrestin mutants. These findings suggest that beta-arrestins play an integral role in GPCR internalization and thus serve a dual role in the regulation of GPCR function.
Ferguson
S S
SS
Howard Hughes Medical Institute Laboratory, Duke University Medical Center, Durham, NC 27710, USA.
Downey
W E
WE
Colapietro
A M
AM
Barak
L S
LS
Ménard
L
L
Caron
M G
MG
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000941:Antigens / Q000235:genetics / Q000502:physiology*; D019390:Arrestins; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary; D005136:Eye Proteins / Q000235:genetics / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D017354:Point Mutation; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D051552:beta-Adrenergic Receptor Kinases; D000071557:beta-Arrestins
D000318:Adrenergic beta-Agonists; D000941:Antigens; D019390:Arrestins; D018076:DNA, Complementary; D005136:Eye Proteins; D018343:Receptors, Adrenergic, beta-2; D000071557:beta-Arrestins; D017868:Cyclic AMP-Dependent Protein Kinases; D051552:beta-Adrenergic Receptor Kinases; D019204:GTP-Binding Proteins; D007545:Isoproterenol