β-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, ie. 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-l-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.