beta-arrestins regulate mitogenic signaling and clathrin-mediated endocytosis of the insulin-like growth factor I receptor.
beta-Arrestins mediate agonist-dependent desensitization of G protein-coupled receptors and target the receptors to clathrin-coated pits for internalization. Here we report an expanded role of beta-arrestins in promoting clathrin-mediated endocytosis of a tyrosine kinase growth factor receptor, i.e. the insulin-like growth factor I (IGF-1) receptor. beta-Arrestins bind to the ligand-occupied IGF-1 receptors, promote their endocytosis, and enhance IGF-1-dependent mitogen-activated protein kinase phosphorylation and DNA synthesis. Our results suggest a role for beta-arrestins in regulating mitogenic signaling and clathrin-mediated endocytosis of receptors not classically coupled to G proteins.
Lin
F T
FT
Howard Hughes Medical Institute, Departments of Medicine and Biochemistry, Duke University Medical Center, Durham, North Carolina 27710, USA.
Daaka
Y
Y
Lefkowitz
R J
RJ
D019390:Arrestins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D002966:Clathrin / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis; D004705:Endocytosis; D006801:Humans; D010766:Phosphorylation; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D000071557:beta-Arrestins
D019390:Arrestins; D002966:Clathrin; D011994:Recombinant Proteins; D000071557:beta-Arrestins; D004247:DNA; D017526:Receptor, IGF Type 1; D017871:Calcium-Calmodulin-Dependent Protein Kinases