SLP-76 Is a Direct Substrate of SHP-1 Recruited to Killer Cell Inhibitory Receptors

Activation of immune system cells via antigen-, Fc-, or natural killer cell-triggering-receptor stimulation is aborted by co-engagement of inhibitory receptors. Negative signaling by killer cell inhibitory receptors and related receptors depends on the Src homology 2 (SH2)-containing protein tyrosin...

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Bibliographic Details
Published in:The Journal of biological chemistry 1998-10, Vol.273 (42), p.27518-27523
Main Authors: Binstadt, Bryce A., Billadeau, Daniel D., Jevremović, Dragan, Williams, Brandi L., Fang, Nan, Yi, Taolin, Koretzky, Gary A., Abraham, Robert T., Leibson, Paul J.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Catalytic Domain
Cytotoxicity Tests, Immunologic
Cytotoxicity, Immunologic
Humans
Intracellular Signaling Peptides and Proteins
Killer Cells, Natural - immunology
Phosphopeptides - metabolism
Phosphoproteins - metabolism
Protein Tyrosine Phosphatase, Non-Receptor Type 11
Protein Tyrosine Phosphatase, Non-Receptor Type 6
Protein Tyrosine Phosphatases - metabolism
Receptors, Immunologic - metabolism
Receptors, KIR
SH2 Domain-Containing Protein Tyrosine Phosphatases
Signal Transduction
Substrate Specificity
T-Lymphocytes, Cytotoxic - immunology
Vaccinia virus - immunology
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Summary:Activation of immune system cells via antigen-, Fc-, or natural killer cell-triggering-receptor stimulation is aborted by co-engagement of inhibitory receptors. Negative signaling by killer cell inhibitory receptors and related receptors depends on the Src homology 2 (SH2)-containing protein tyrosine phosphatase SHP-1. Using a combination of direct binding and functional assays, we demonstrated that the SH2 domain-containing leukocyte protein 76 (SLP-76) is a specific target for dephosphorylation by SHP-1 in T cells and natural killer cells. Furthermore, we showed that tyrosine-phosphorylated SLP-76 is required for optimal activation of cytotoxic lymphocytes, suggesting that the targeted dephosphorylation of SLP-76 by SHP-1 is an important mechanism for the negative regulation of immune cell activation by inhibitory receptors.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.273.42.27518