Fig. 3. Proposed roles of ß-arrestin-dependent recruitment of Src kinases in GPCR signaling. The binding of ß-arrestins to agonist-occupied GPCRs coincides with the recruitment of Src family tyrosine kinases, including c-Src, Hck and c-Fgr (Src-TK), to the receptor—ß-arrestin complex. Several signaling events have been reported to involve ß-arrestin-dependent Src recruitment. These include the regulation of clathrin-dependent ß2-adrenergic receptor endocytosis by tyrosine phosphorylation of dynamin (1), Ras-dependent activation of the ERK1/2 MAP kinase cascade and stimulation of cell proliferation by ß2-adrenergic and neurokinin NK1 receptors (2), and stimulation of chemokine CXCR1 receptor-mediated neutrophil degranulation (3).