Abstract
An emerging family of cell surface inhibitory receptors is characterized by the presence of intracytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIM). These ITIM-bearing inhibitory receptors, which are typically paired with activating isoforms, associate with Src homology domain 2-containing phosphatases following ITIM tyrosine phosphorylation. Two categories of phosphatases are recruited by the ITIM-bearing receptors: the protein-tyrosine phosphatases, SHP-1 and SHP-2, and the polyphosphate inositol 5-phosphatase, SHIP. The dynamic equilibrium of B cell activation is partially controlled by two well known ITIM-bearing receptors, CD22 and FcgammaRIIB, a low affinity receptor for IgG. We describe here that a murine ITIM-bearing molecule, PIR-B, can also negatively regulate B cell activation. Tyrosine-phosphorylated ITIMs allow PIR-B to associate with SHP-1 but not with SHIP. Engagement of PIR-B thereby initiates a SHP-1-dependent inhibitory pathway that may play an important role in regulating B lymphocyte activation.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antibodies, Monoclonal
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Binding Sites
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Intracellular Signaling Peptides and Proteins
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Kinetics
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Mice
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Molecular Sequence Data
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / metabolism*
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Rats
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Receptors, IgG / biosynthesis
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Receptors, IgG / physiology
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / immunology
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Receptors, Immunologic / physiology*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / immunology
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Recombinant Fusion Proteins / metabolism
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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Serotonin / metabolism
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Transfection
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Tumor Cells, Cultured
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src Homology Domains
Substances
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Antibodies, Monoclonal
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Intracellular Signaling Peptides and Proteins
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Peptide Fragments
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Pirb protein, mouse
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Pirb protein, rat
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Receptors, IgG
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Receptors, Immunologic
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Recombinant Fusion Proteins
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Serotonin
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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Ptpn11 protein, rat
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Ptpn6 protein, mouse
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Ptpn6 protein, rat
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SH2 Domain-Containing Protein Tyrosine Phosphatases