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

Bryce A. Binstadt, Daniel D Billadeau, Dragan Jevremovic, Brandi L. Williams, Nan Fang, Taolin Yi, Gary A. Koretzky, Robert T. Abraham, Paul J. Leibson

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)27518-27523
Number of pages6
JournalJournal of Biological Chemistry
Volume273
Issue number42
DOIs
StatePublished - Oct 16 1998

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KIR Receptors
src Homology Domains
Leukocytes
Chemical activation
Non-Receptor Type 11 Protein Tyrosine Phosphatase
Substrates
Non-Receptor Type 6 Protein Tyrosine Phosphatase
Natural Killer Cell Receptors
Proteins
T-cells
Lymphocytes
Immune system
Lymphocyte Activation
Natural Killer Cells
Tyrosine
Immune System
Assays
T-Lymphocytes
Antigens

ASJC Scopus subject areas

  • Biochemistry

Cite this

SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. / Binstadt, Bryce A.; Billadeau, Daniel D; Jevremovic, Dragan; Williams, Brandi L.; Fang, Nan; Yi, Taolin; Koretzky, Gary A.; Abraham, Robert T.; Leibson, Paul J.

In: Journal of Biological Chemistry, Vol. 273, No. 42, 16.10.1998, p. 27518-27523.

Research output: Contribution to journalArticle

Binstadt, BA, Billadeau, DD, Jevremovic, D, Williams, BL, Fang, N, Yi, T, Koretzky, GA, Abraham, RT & Leibson, PJ 1998, 'SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors', Journal of Biological Chemistry, vol. 273, no. 42, pp. 27518-27523. https://doi.org/10.1074/jbc.273.42.27518
Binstadt, Bryce A. ; Billadeau, Daniel D ; Jevremovic, Dragan ; Williams, Brandi L. ; Fang, Nan ; Yi, Taolin ; Koretzky, Gary A. ; Abraham, Robert T. ; Leibson, Paul J. / SLP-76 is a direct substrate of SHP-1 recruited to killer cell inhibitory receptors. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 42. pp. 27518-27523.
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