Published online before print May 22, 2003

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© 2003 by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi: 10.1189/jlb.0902454

Received for publication September 12, 2002.
Revised November 12, 2002.
Accepted for publication November 22, 2002.

Article

The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fc receptors FcRIIB and FcRIIA

University of Pennsylvania School of Medicine, Philadelphia

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

Abstract

Inositol and tyrosine phosphatases have been implicated in Fc receptor for immunoglobulin G (FcR)IIB inhibitory signals in B cells, mast cells, and monocytes. Here, we propose a role for the Src homology 2 (SH2)-containing tyrosine phosphatase-1 (SHP-1) in FcRIIB-mediated inhibition of FcR signaling. Coexpression of SHP-1 enhances FcRIIB-mediated inhibition of FcRIIA phagocytosis in COS-1 cells. SHP-1 also enhances the reduction in FcRIIA tyrosine phosphorylation that accompanies this inhibition. Significantly, tyrosine phosphorylation of Syk kinase is substantially inhibited by SHP-1. Furthermore, the activation of SHP-1 tyrosine phosphorylation is observed following stimulation of FcRII in COS-1 cells and in human monocytes. The SH2 domain containing inositol polyphosphate phosphatase (SHIP)-1 also enhances FcRIIB-mediated inhibition of FcRIIA, indicating that FcRIIB can use more than one pathway for its inhibitory action. In addition, SHP-1 and SHIP-1 can inhibit FcRIIA phagocytosis and signal transduction in the absence of FcRIIB. The data support emerging evidence that SH2-containing phosphatases, such as SHP-1 and SHIP-1, can modulate signaling by "activating" receptors.

Key Words: phagocytosis • tyrosine phosphorylation • inhibition

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