Figure 3.

IGF-IR can form functional RTK/GPCR hybrids, thus aggregating tyrosine kinase and GPCR signaling. Ligand-dependent activation of classical kinase-dependent signaling with β-arrestin recruitment provokes GRK-dependent serine phosphorylation located in the IGF-IR C-domain. β-arrestin activates kinase desensitization and ubiquitination and initiates kinase-independent signaling through MAPK. Adapted from Worrall et al. Novel Mechanisms of Regulation of IGF-1R Action: Functional and Therapeutic Implications. Pediatr Endocrinol Rev. 2013 10:473-484.