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The effect of phosphatases SHP‐1 and SHIP‐1 on signaling by the ITIM‐ and ITAM‐containing Fcγ receptors FcγRIIB and FcγRIIA
Author(s) -
Huang ZhenYu,
Hunter Sharon,
Kim MooKyung,
Indik Zena K.,
Schreiber Alan D.
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0902454
Subject(s) - biology , receptor , phosphatase , signal transduction , microbiology and biotechnology , biochemistry , immunology , phosphorylation
Inositol and tyrosine phosphatases have been implicated in inhibitory signaling by an Fc receptor for immunoglobulin G, FcγRIIB, 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 FcγRIIB‐mediated inhibition of FcγR signaling. Coexpression of SHP‐1 enhances FcγRIIB‐mediated inhibition of FcγRIIA phagocytosis in COS‐1 cells. SHP‐1 also enhances the reduction in FcγRIIA 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 FcγRII in COS‐1 cells and in human monocytes. The SH2 domain containing inositol phosphatase (SHIP), SHIP‐1 also enhances FcγRIIB‐mediated inhibition of FcγRIIA, indicating that FcγRIIB can use more than one pathway for its inhibitory action. In addition, SHP‐1 and SHIP‐1 can inhibit FcγRIIA phagocytosis and signal transduction in the absence of FcγRIIB. The data support emerging evidence that SH2‐containing phosphatases, such as SHP‐1 and SHIP‐1, can modulate signaling by “activating” receptors.