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J. Biol. Chem., Vol. 277, Issue 43, 41287-41293, October 25, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/43/41287    most recent M207835200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Edberg, J. C. Articles by Kimberly, R. P. Search for Related Content PubMed PubMed Citation Articles by Edberg, J. C. Articles by Kimberly, R. P. Social Bookmarking                      What's this?

The CY Domain of the FcRIa -Chain (CD64) Alters -Chain Tyrosine-based Signaling and Phagocytosis^*

Jeffrey C. Edberg^§¶, Hongwei Qin^§, Andrew W. Gibson, Arthur M. F. Yee, Patricia B. Redecha, Zena K. Indik^**, Alan D. Schreiber^**, and Robert P. Kimberly

From the  Departments of Medicine and Microbiology, The University of Alabama at Birmingham, Birmingham, Alabama 35294,  Department of Medicine, Hospital for Special Surgery and Weill Medical College of Cornell University, New York, New York 10021, and ^** Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104

Although the cytoplasmic domain of the human FcRIa -chain lacks tyrosine-based phosphorylation motifs, it modulates receptor cycling and receptor-specific cytokine production. The cytoplasmic domain of FcRIa is constitutively phosphorylated, and the inhibition of dephosphorylation with okadaic acid, an inhibitor of type 1 and type 2A protein serine/threonine phosphatase, inhibits both receptor-induced activation of the early tyrosine phosphorylation cascade and receptor-specific phagocytosis. To explore the basis for these effects of the cytoplasmic domain of FcRIa, we developed a series of human FcRIa molecular variants, expressed in the murine macrophage cell line P388D1, and demonstrate that serine phosphorylation of the cytoplasmic domain is an important regulatory mechanism. Truncation of the cytoplasmic domain and mutation of the cytoplasmic domain serine residues to alanine abolish the okadaic acid inhibition of phagocytic function. In contrast, the serine mutants did not recapitulate the selective effects of cytoplasmic domain truncation on cytokine production. These results demonstrate for the first time a direct functional role for serine phosphorylation in the -chain of FcRIa and suggest that the cytoplasmic domain of FcRI regulates the different functional capacities of the FcRIa-receptor complex.

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