SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors

J Biol Chem. 1998 Oct 16;273(42):27518-23. doi: 10.1074/jbc.273.42.27518.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 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

Substances

  • Adaptor Proteins, Signal Transducing
  • Intracellular Signaling Peptides and Proteins
  • Phosphopeptides
  • Phosphoproteins
  • Receptors, Immunologic
  • Receptors, KIR
  • SLP-76 signal Transducing adaptor proteins
  • PTPN11 protein, human
  • PTPN6 protein, human
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • SH2 Domain-Containing Protein Tyrosine Phosphatases