Mitogen-activated protein kinase activity is involved in effector functions triggered by the CD94/NKG2-C NK receptor specific for HLA-E.
The CD94/NKG2C heterodimer constitutes an activating receptor involved in NK cell-mediated recognition of the class lb molecule HLA-E. It transduces the triggering signal through an ITAM-bearing molecule, DAP12/KARAP, coupled non-covalently to the receptor. Here we show that specific engagement of the receptor complex expressed on the surface of an NK clone induced the phosphorylation of mitogen-activated protein kinase (MAPK). By the use of the MEK inhibitor PD098059 we demonstrate that the MAPK pathway participates in the CD94-dependent TNF-alpha production and cytotoxicity. Moreover, we transferred the activating function by transfection of the heterologous RBL cell line with CD94/NKG2-C/DAP12. In this system, cross-linking of the receptor induced calcium mobilization, serotonin release and phosphorylation of MAPK.
Carretero
M
M
Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Spain.
Llano
M
M
Navarro
F
F
Bellón
T
T
López-Botet
M
M
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004792:Enzyme Precursors / Q000502:physiology; D005419:Flavonoids / Q000494:pharmacology; D006680:HLA Antigens / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007694:Killer Cells, Natural / Q000201:enzymology / Q000276:immunology*; D037181:Lectins, C-Type; D015471:Leukemia, Basophilic, Acute / Q000473:pathology; D020935:MAP Kinase Signaling System; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D051381:Rats; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins / Q000276:immunology; D012701:Serotonin / Q000378:metabolism; D000072377:Syk Kinase; D014162:Transfection; D014407:Tumor Cells, Cultured; D000097625:HLA-E Antigens
D048868:Adaptor Proteins, Signal Transducing; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D004792:Enzyme Precursors; D005419:Flavonoids; D006680:HLA Antigens; D015395:Histocompatibility Antigens Class I; D047908:Intracellular Signaling Peptides and Proteins; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D011505:Protein-Tyrosine Kinases; D011971:Receptors, Immunologic; D055607:Receptors, Natural Killer Cell; D011993:Recombinant Fusion Proteins; D012701:Serotonin; D000072377:Syk Kinase; D000097625:HLA-E Antigens; C527054:KLRC1 protein, human; C527059:KLRC2 protein, human; C497869:KLRD1 protein, human; C497871:Klrd1 protein, rat; C110546:TYROBP protein, human; C000606896:SYK protein, human; C000606898:Syk protein, rat; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one