Published online before print May 10, 2004

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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1103562

Received for publication November 13, 2003.
Revised March 3, 2004.
Accepted for publication April 6, 2004.

Article

The monocyte Fc receptors FcRI/ and FcRIIA differ in their interaction with Syk- and Src-related tyrosine kinases

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

^@ To whom correspondence should be addressed. E-mail: schreibr{at}mail.med.upenn.edu.

Abstract

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

Key Words: ITAM • COS-1 • immunoglobulin • red blood cells

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