TYROSINE PHOSPHORYLATION OF A HUMAN KILLER INHIBITORY RECEPTOR RECRUITS PROTEIN-TYROSINE-PHOSPHATASE 1C

Natural killer (NK) cells express killer inhibitory receptors that med iate negative regulation of NK cell cytotoxicity upon binding to MHC c lass I molecules on target cells, Unrelated inhibitory receptors on B cells have recently been shown to function through recruitment of phos photyrosine phosphatase 1C (PTP-1C). Here, we show that a human killer inhibitory receptor specific for HLA-C also recruits PTP-1C after pho sphorylation induced either by the pharmacological agent phenylarsine oxide or by conjugation with target cells. This recruitment is mediate d by the binding of specific cytoplasmic phosphotyrosine-containing se quences to PTP-1C. These results implicate PTP-1C as a cytosolic compo nent of the negative signaling pathway through NK cell inhibitory rece ptors.