HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahamed, J. Articles by Ali, H. Search for Related Content PubMed PubMed Citation Articles by Ahamed, J. Articles by Ali, H.

Cutting Edge: Differential Regulation of Chemoattractant Receptor-Induced Degranulation and Chemokine Production by Receptor Phosphorylation¹

Jasimuddin Ahamed^*, Bodduluri Haribabu and Hydar Ali^2,*

^* Department of Pathology, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA 19104; and Department of Pathology and the James Graham Brown Cancer Center, University of Louisville School of Medicine, Louisville, KY 40202

Phosphorylation of G protein-coupled receptors and the subsequent recruitment of -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 (ST-C3aR). In contrast, C3a caused CCL2 production only in C3aR but not ST-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 ST-C3aR, led to the translocation of green fluorescent protein tagged -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.

This article has been cited by other articles:

				R. T. Venkatesha, J. Ahamed, C. Nuesch, A. K. Zaidi, and H. Ali Platelet-activating Factor-induced Chemokine Gene Expression Requires NF-{kappa}B Activation and Ca2+/Calcineurin Signaling Pathways: INHIBITION BY RECEPTOR PHOSPHORYLATION AND {beta}-ARRESTIN RECRUITMENT J. Biol. Chem., October 22, 2004; 279(43): 44606 - 44612. [Abstract] [Full Text] [PDF]

				I. Hecht, L. Cahalon, R. Hershkoviz, A. Lahat, S. Franitza, and O. Lider Heterologous desensitization of T cell functions by CCR5 and CXCR4 ligands: inhibition of cellular signaling, adhesion and chemotaxis Int. Immunol., January 1, 2003; 15(1): 29 - 38. [Abstract] [Full Text] [PDF]

				C. M. Vines, M. Xue, D. C. Maestas, D. F. Cimino, and E. R. Prossnitz Regulation of N-Formyl Peptide-Mediated Degranulation by Receptor Phosphorylation J. Immunol., December 15, 2002; 169(12): 6760 - 6766. [Abstract] [Full Text] [PDF]

				J. Ahamed and H. Ali Distinct Roles of Receptor Phosphorylation, G Protein Usage, and Mitogen-activated Protein Kinase Activation on Platelet Activating Factor-induced Leukotriene C4 Generation and Chemokine Production J. Biol. Chem., June 14, 2002; 277(25): 22685 - 22691. [Abstract] [Full Text] [PDF]

				S. A. Cain and P. N. Monk The Orphan Receptor C5L2 Has High Affinity Binding Sites for Complement Fragments C5a and C5a des-Arg74 J. Biol. Chem., February 22, 2002; 277(9): 7165 - 7169. [Abstract] [Full Text] [PDF]