title: Killer cell inhibitory receptor recognition of human leukocyte antigen (HLA) class I blocks formation of a pp36/PLC-gamma signaling complex in human natural killer (NK) cells.
abstract: The killer cell inhibitory receptors (KIR) of human natural killer (NK) cells recognize human leukocyte antigen class I molecules and inhibit NK cell cytotoxicity through their interaction with protein tyrosine phosphatases (PTP). Here, we report that KIR recognition of class I ligands inhibits distal signaling events and ultimately NK cell cytotoxicity by blocking the association of an adaptor protein (pp36) with phospholipase C-gamma in NK cells. In addition, we demonstrate that pp36 can serve as a substrate in vitro for the KIR-associated PTP, PTP-1C (also called SHP-1), and that recognition of class I partially disrupts tyrosine phosphorylation of NK cell proteins, providing evidence for KIR-induced phosphatase activity.
authors.affiliation: Department of Structural Biology, Stanford University Medical School, California 94305, USA.
authors.forename: N M
authors.initials: NM
authors.lastname: Valiante
authors.forename: J H
authors.initials: JH
authors.lastname: Phillips
authors.forename: L L
authors.initials: LL
authors.lastname: Lanier
authors.forename: P
authors.initials: P
authors.lastname: Parham
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D002118:Calcium / Q000378:metabolism; D051380:GRB2 Adaptor Protein; D015235:HLA-B Antigens / Q000276:immunology / Q000502:physiology*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology / Q000502:physiology*; D007700:Kinetics; D019000:Phosphotyrosine / Q000032:analysis; D011493:Protein Kinase C / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology / Q000502:physiology*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051380:GRB2 Adaptor Protein; C495948:GRB2 protein, human; D015235:HLA-B Antigens; D007527:Isoenzymes; D011506:Proteins; D011971:Receptors, Immunologic; D019000:Phosphotyrosine; D015544:Inositol 1,4,5-Trisphosphate; C087857:protein kinase C gamma; D011493:Protein Kinase C; D002118:Calcium