β-Arrestins Regulate Mitogenic Signaling and Clathrin-mediated Endocytosis of the Insulin-like Growth Factor I Receptor*

β-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 β-arrestins in promoting clathrin-mediated endocytosis of a tyrosine kinase growth factor receptor, i.e. the insulin-like growth factor I (IGF-1) receptor. β-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 β-arrestins in regulating mitogenic signaling and clathrin-mediated endocytosis of receptors not classically coupled to G proteins.

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