Cutting edge: Differential regulation of chemoattractant receptor-induced degranulation and chemokine production by receptor phosphorylation.
Phosphorylation of G protein-coupled receptors and the subsequent recruitment of beta-arrestin play an important role in desensitization of receptor-mediated responses, including degranulation in leukocytes. In this study, we report that receptor phosphorylation also provides a stimulatory signal for CCR ligand 2 (CCL2) production. C3a stimulated degranulation in a basophilic leukemia RBL-2H3 cell expressing wild-type C3aR or a phosphorylation-deficient mutant (DeltaST-C3aR). In contrast, C3a caused CCL2 production only in C3aR but not DeltaST-C3aR cells. Furthermore, overexpression of G protein-coupled receptor kinase 2 resulted in enhancement of both ligand-induced receptor phosphorylation and CCL2 production but inhibition of degranulation. Agonist activation of C3aR, but not DeltaST-C3aR, led to the translocation of green fluorescent protein tagged beta-arrestin 2 from the cytoplasm to the plasma membrane. These data demonstrate that receptor phosphorylation, which provides a turn off signal for degranulation, is essential for CCL2 production.
Ahamed
J
J
Department of Pathology, School of Dental Medicine, University of Pennsylvania, 4010 Locust Street, Philadelphia, PA 19104, USA.
Haribabu
B
B
Ali
H
H
D000595:Amino Acid Sequence; D000818:Animals; D015550:Cell Degranulation; D018932:Chemokine CCL2 / Q000096:biosynthesis*; D015926:Complement C3a / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics / Q000502:physiology; D054769:G-Protein-Coupled Receptor Kinase 2; D020962:Heterotrimeric GTP-Binding Proteins / Q000502:physiology; D007962:Leukocytes / Q000276:immunology*; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D010766:Phosphorylation; D051381:Rats; D011951:Receptors, Complement / Q000235:genetics / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured; D051552:beta-Adrenergic Receptor Kinases
D018932:Chemokine CCL2; D008565:Membrane Proteins; D011951:Receptors, Complement; D011971:Receptors, Immunologic; C085567:complement C3a receptor; D015926:Complement C3a; D017868:Cyclic AMP-Dependent Protein Kinases; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2; D020962:Heterotrimeric GTP-Binding Proteins