Tyrosine phosphorylation of a human killer inhibitory receptor recruits protein tyrosine phosphatase 1C.
Natural killer (NK) cells express killer inhibitory receptors that mediate negative regulation of NK cell cytotoxicity upon binding to MHC class I molecules on target cells. Unrelated inhibitory receptors on B cells have recently been shown to function through recruitment of phosphotyrosine phosphatase 1C (PTP-1C). Here, we show that a human killer inhibitory receptor specific for HLA-C also recruits PTP-1C after phosphorylation induced either by the pharmacological agent phenylarsine oxide or by conjugation with target cells. This recruitment is mediated by the binding of specific cytoplasmic phosphotyrosine-containing sequences to PTP-1C. These results implicate PTP-1C as a cytosolic component of the negative signaling pathway through NK cell inhibitory receptors.
Campbell
K S
KS
Basel Institute for Immunology, Switzerland.
Dessing
M
M
Lopez-Botet
M
M
Cella
M
M
Colonna
M
M
D000595:Amino Acid Sequence; D002118:Calcium / Q000502:physiology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004789:Enzyme Activation; D015236:HLA-C Antigens / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000502:physiology*; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000378:metabolism*; D015398:Signal Transduction
D015236:HLA-C Antigens; D047908:Intracellular Signaling Peptides and Proteins; D010455:Peptides; D011971:Receptors, Immunologic; D019000:Phosphotyrosine; C516724:PTPN11 protein, human; C509249:PTPN6 protein, human; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; D002118:Calcium