Cutting edge: Differential regulation of chemoattractant receptor-induced degranulation and chemokine production by receptor phosphorylation

Phosphorylation of G protein-coupled receptors and the subsequent recruitme nt of beta -arrestin play an important role in desensitization of receptor- mediated responses, including degranulation in leukocytes. In this study, w e report that receptor phosphorylation also provides a stimulatory signal f or CCR ligand 2 (CCL2) production. C3a stimulated degranulation in a basoph ilic leukemia RBL-2H3 cell expressing wildtype C3aR or a phosphorylation-de ficient mutant (Delta ST-C3aR). In contrast, C3a caused CCL2 production onl y in C3aR but not Delta ST-C3aR cells. Furthermore, overexpression of G pro tein-coupled receptor kinase 2 resulted in enhancement of both ligand-induc ed receptor phosphorylation and CCL2 production but inhibition of degranula tion. Agonist activation of C3aR, but not Delta ST-C3aR, led to the translo cation of green fluorescent protein tagged beta -arrestin 2 from the cytopl asm to the plasma membrane. These data demonstrate that receptor phosphoryl ation, which provides a turn off signal for degranulation, is essential for CCL2 production.