Journal of Leukocyte Biology
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Originally published online as doi:10.1189/jlb.1103562 on May 10, 2004

Published online before print May 10, 2004
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(Journal of Leukocyte Biology. 2004;76:491-499.)
© 2004 by Society for Leukocyte Biology

The monocyte Fc{gamma} receptors Fc{gamma}RI/{gamma} and Fc{gamma}RIIA differ in their interaction with Syk and with Src-related tyrosine kinases

Zhen-Yu Huang, Sharon Hunter, Moo-Kyung Kim, Paul Chien, Randall G. Worth, Zena K. Indik and Alan D. Schreiber1

University of Pennsylvania School of Medicine, Hematology and Oncology Division, Philadelphia

1Correspondence: University of Pennsylvania School of Medicine, Hematology and Oncology Division, Biomedical Research Building II/III, Room 705, 421 Curie Blvd., Philadelphia, PA 19104. E-mail: schreibr{at}mail.med.upenn.edu

There are important differences in signaling between the Fc receptor for immunoglobulin G (IgG) Fc{gamma}RIIA, which uses the Ig tyrosine-activating motif (ITAM) within its own cytoplasmic domain, and Fc{gamma}RI, which transmits signals by means of an ITAM located within the cytoplasmic domain of its associated {gamma}-chain. For example, in transfected epithelial cells and COS-1 cells, Fc{gamma}RIIA mediates phagocytosis of IgG-coated red blood cells more efficiently than does Fc{gamma}RI/{gamma}, and enhancement of phagocytosis by Syk kinase is more pronounced for Fc{gamma}RI/{gamma} than for Fc{gamma}RIIA. In addition, structure/function studies indicate that the {gamma}-chain ITAM and the Fc{gamma}RIIA ITAM have different requirements for mediating the phagocytic signal. To study the differences between Fc{gamma}RIIA and Fc{gamma}RI/{gamma}, we examined the interaction of Fc{gamma}RIIA and the Fc{gamma}RI/{gamma} chimera Fc{gamma}RI-{gamma}-{gamma} (extracellular domain–transmembrane domain–cytoplasmic domain) with Syk kinase and with the Src-related tyrosine kinases (SRTKs) Hck and Lyn in transfected COS-1 cells. Our data indicate that Fc{gamma}RIIA interacts more readily with Syk than does Fc{gamma}RI-{gamma}-{gamma} and suggest that one consequence may be the greater phagocytic efficiency of Fc{gamma}RIIA compared with Fc{gamma}RI/{gamma}. Furthermore, individual SRTKs affect the efficiency of phagocytosis differently for Fc{gamma}RI-{gamma}-{gamma} and Fc{gamma}RIIA and also influence the ability of these receptors to interact with Syk kinase. Taken together, the data suggest that differences in signaling by Fc{gamma}RIIA and Fc{gamma}RI-{gamma}-{gamma} are related in part to interaction with Syk and Src kinases and that individual SRTKs play different roles in Fc{gamma}R-mediated phagocytosis.

Key Words: ITAM • phagocytosis • Hck




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