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

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作者：

BA Binstadt，DD Billadeau，D Jevremovic，BL Williams，N Fang，T Yi，GA Koretzky，RT Abraham，PJ Leibson

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摘要：

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.

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关键词：

Killer Cells, Natural Phosphoproteins Protein-Tyrosine-Phosphatase Receptors, Immunologic 杀伤细胞, 天然磷蛋白类蛋白质酪氨酸磷酸酶受体, 免疫 T淋巴细胞, 细胞毒性