Abstract
The SH2 domain-containing cytoplasmic protein tyrosine phosphatase, SHP-1, negatively regulates hematopoietic cell signaling. SHP-1 is associated with a tyrosine phosphorylated, plasma membrane-spanning glycoprotein, pp130, in colony stimulating factor-1 stimulated or unstimulated macrophages. This association is phosphotyrosine dependent and is mediated by the amino-terminal SH2 domain of SHP-1. pp130 behaves as a substrate of SHP-1 in vitro and is hyperphosphorylated on tyrosine in SHP-1 deficient macrophages from viable-motheaten mice. Co-immunoprecipitation data indicate that pp130 is the product of the mouse p91/PIR-B gene that encodes a member of the killer cell inhibitory receptor (KIR)/leukocyte immunoglobulin-like receptor (LIR) family. By analogy to the KIRs, p91/PIR-B may represent a novel class of macrophage receptors which act to suppress macrophage activation. These observations identify SHP-1 interactions with and regulation of p91/PIR-B as a potential mechanism for inhibiting the signaling cascades linking extracellular stimuli to macrophage activation and/or development.
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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Antigens, CD*
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Intracellular Signaling Peptides and Proteins
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Leukocyte Immunoglobulin-like Receptor B1
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Macrophages / metabolism*
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Mice
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Molecular Sequence Data
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Multigene Family
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Nuclear Proteins / metabolism
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Phosphoproteins / metabolism
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Phosphorylation
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Phosphotyrosine / physiology
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Protein Binding
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Protein Processing, Post-Translational
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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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Receptors, Immunologic / genetics
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Receptors, Immunologic / metabolism*
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Receptors, KIR
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SH2 Domain-Containing Protein Tyrosine Phosphatases
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Signal Transduction
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src Homology Domains*
Substances
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Antigens, CD
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Intracellular Signaling Peptides and Proteins
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LILRB1 protein, human
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Leukocyte Immunoglobulin-like Receptor B1
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Nuclear Proteins
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Phosphoproteins
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Pirb protein, mouse
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Receptors, Immunologic
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Receptors, KIR
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nucleolar phosphoprotein p130
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Phosphotyrosine
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PTPN11 protein, human
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PTPN6 protein, human
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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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Ptpn6 protein, mouse
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SH2 Domain-Containing Protein Tyrosine Phosphatases