Entry Name Natural killer cell mediated cytotoxicity - Ursus arctos horribilis (North American brown bear)
Description Natural killer (NK) cells are lymphocytes of the innate immune system that are involved in early defenses against both allogeneic (nonself) cells and autologous cells undergoing various forms of stress, such as infection with viruses, bacteria, or parasites or malignant transformation. Although NK cells do not express classical antigen receptors of the immunoglobulin gene family, such as the antibodies produced by B cells or the T cell receptor expressed by T cells, they are equipped with various receptors whose engagement allows them to discriminate between target and nontarget cells. Activating receptors bind ligands on the target cell surface and trigger NK cell activation and target cell lysis. However Inhibitory receptors recognize MHC class I molecules (HLA) and inhibit killing by NK cells by overruling the actions of the activating receptors. This inhibitory signal is lost when the target cells do not express MHC class I and perhaps also in cells infected with virus, which might inhibit MHC class I exprssion or alter its conformation. The mechanism of NK cell killing is the same as that used by the cytotoxic T cells generated in an adaptive immune response; cytotoxic granules are released onto the surface of the bound target cell, and the effector proteins they contain penetrate the cell membrane and induce programmed cell death.
Class Organismal Systems; Immune systemBRITE hierarchy
Pathway map uah04650 Natural killer cell mediated cytotoxicity
Ortholog table Other DBs Organism Ursus arctos horribilis (North American brown bear) [GN:
uah ]
Gene 113247403 LOW QUALITY PROTEIN: killer cell immunoglobulin-like receptor 3DL3 [KO:K07980 ]
113257892 NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541 ]
113266577 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
113241811 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
113261702 CSF2; granulocyte-macrophage colony-stimulating factor isoform X1 [KO:K05427 ]
113244840 TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992 ]
113268656 low affinity immunoglobulin gamma Fc region receptor III-B-like isoform X1 [KO:K06463 ]
113247364 leukocyte immunoglobulin-like receptor subfamily B member 3A [KO:K06741 ]
113246719 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983 ]
113262884 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
113267622 LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362 ]
113267780 LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356 ]
113258609 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
113254799 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113270537 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113253989 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113256705 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113254730 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
113255266 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
113257895 NKG2-D type II integral membrane protein-like isoform X1 [KO:K06728 ]
113244836 HCST; hematopoietic cell signal transducer isoform X1 [KO:K07988 ]
113270001 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113259177 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113263105 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113253544 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
113258729 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
113255024 TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721 ]
113262825 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
113258968 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
Compound C01245 D-myo-Inositol 1,4,5-trisphosphate
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference Authors Chiesa S, Tomasello E, Vivier E, Vely F.
Title Coordination of activating and inhibitory signals in natural killer cells.
Journal Reference Authors Maghazachi AA.
Title Insights into seven and single transmembrane-spanning domain receptors and their signaling pathways in human natural killer cells.
Journal Reference Authors Vivier E, Nunes JA, Vely F.
Title Natural killer cell signaling pathways.
Journal Reference Authors Colucci F, Di Santo JP, Leibson PJ.
Title Natural killer cell activation in mice and men: different triggers for similar weapons?
Journal Reference Authors Perussia B.
Title Signaling for cytotoxicity.
Journal Reference Authors Smyth MJ, Cretney E, Kelly JM, Westwood JA, Street SE, Yagita H, Takeda K, van Dommelen SL, Degli-Esposti MA, Hayakawa Y.
Title Activation of NK cell cytotoxicity.
Journal Reference Authors Djeu JY, Jiang K, Wei S.
Title A view to a kill: signals triggering cytotoxicity.
Journal Clin Cancer Res 8:636-40 (2002)
Reference Authors Smyth MJ, Takeda K, Hayakawa Y, Peschon JJ, van den Brink MR, Yagita H.
Title Nature's TRAIL--on a path to cancer immunotherapy.
Journal Reference Authors Colonna M.
Title Fine-tuning NK cell responses: it's a family affair.
Journal Reference Authors Bonnema JD, Leibson PJ.
Title Signal transduction during NK cell activation.
Journal Chem Immunol 64:28-43 (1996)
Reference Authors Tassi I, Presti R, Kim S, Yokoyama WM, Gilfillan S, Colonna M.
Title Phospholipase C-gamma 2 is a critical signaling mediator for murine NK cell activating receptors.
Journal Reference Authors Rao A, Luo C, Hogan PG.
Title Transcription factors of the NFAT family: regulation and function.
Journal Reference Authors Wu J, Lanier LL.
Title Natural killer cells and cancer.
Journal Reference Authors Cerwenka A, Lanier LL.
Title Natural killer cells, viruses and cancer.
Journal Reference Authors Blott EJ, Griffiths GM.
Title Secretory lysosomes.
Journal Reference Authors Lieberman J.
Title The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal.
Journal Reference Authors Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
Title Granzyme B: a natural born killer.
Journal Reference Authors Liu D, Xu L, Yang F, Li D, Gong F, Xu T.
Title Rapid biogenesis and sensitization of secretory lysosomes in NK cells mediated by target-cell recognition.
Journal Reference Authors Trotta R, Puorro KA, Paroli M, Azzoni L, Abebe B, Eisenlohr LC, Perussia B.
Title Dependence of both spontaneous and antibody-dependent, granule exocytosis-mediated NK cell cytotoxicity on extracellular signal-regulated kinases.
Journal J Immunol 161:6648-56 (1998)
Reference Authors Jevremovic D, Billadeau DD, Schoon RA, Dick CJ, Leibson PJ.
Title Regulation of NK cell-mediated cytotoxicity by the adaptor protein 3BP2.
Journal Related uah04060 Cytokine-cytokine receptor interaction
KO pathway LinkDB All DBs
