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

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

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


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
Issue number42
StatePublished - Oct 16 1998


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