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. 2003 Jun;73(6):823-9.
doi: 10.1189/jlb.0902454.

The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcgamma receptors FcgammaRIIB and FcgammaRIIA

Zhen-Yu Huang  1 , Sharon Hunter, Moo-Kyung Kim, Zena K Indik, Alan D Schreiber
Affiliations

The effect of phosphatases SHP-1 and SHIP-1 on signaling by the ITIM- and ITAM-containing Fcgamma receptors FcgammaRIIB and FcgammaRIIA

Zhen-Yu Huang et al. J Leukoc Biol. 2003 Jun.

Abstract

Inositol and tyrosine phosphatases have been implicated in inhibitory signaling by an Fc receptor for immunoglobulin G, FcgammaRIIB, 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 FcgammaRIIB-mediated inhibition of FcgammaR signaling. Coexpression of SHP-1 enhances FcgammaRIIB-mediated inhibition of FcgammaRIIA phagocytosis in COS-1 cells. SHP-1 also enhances the reduction in FcgammaRIIA 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 FcgammaRII in COS-1 cells and in human monocytes. The SH2 domain containing inositol phosphatase (SHIP), SHIP-1 also enhances FcgammaRIIB-mediated inhibition of FcgammaRIIA, indicating that FcgammaRIIB can use more than one pathway for its inhibitory action. In addition, SHP-1 and SHIP-1 can inhibit FcgammaRIIA phagocytosis and signal transduction in the absence of FcgammaRIIB. The data support emerging evidence that SH2-containing phosphatases, such as SHP-1 and SHIP-1, can modulate signaling by "activating" receptors.

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