Entry Name Natural killer cell mediated cytotoxicity - Zalophus californianus (California sea lion)
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 zca04650 Natural killer cell mediated cytotoxicity
Other DBs Organism Zalophus californianus (California sea lion) [GN:
zca ]
Gene 113908122 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
113911688 PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
113916957 TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
113917022 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113917179 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
113918898 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
113919467 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113921804 FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390 ]
113922696 RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860 ]
113924138 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113924414 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
113924761 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
113924764 SH3BP2; LOW QUALITY PROTEIN: SH3 domain-binding protein 2 [KO:K07984 ]
113926172 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
113927325 IFNGR1; LOW QUALITY PROTEIN: interferon gamma receptor 1 [KO:K05132 ]
113927743 NCR3; natural cytotoxicity triggering receptor 3 isoform X1 [KO:K06743 ]
113928897 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
113929387 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
113931754 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
113932499 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983 ]
113932720 LAT; linker for activation of T-cells family member 1 isoform X2 [KO:K07362 ]
113933201 LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356 ]
113933742 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
113934411 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
113935662 HCST; hematopoietic cell signal transducer isoform X1 [KO:K07988 ]
113936670 VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730 ]
113938162 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
113938304 PLCG1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116 ] [EC:3.1.4.11 ]
113939579 GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364 ]
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 zca04060 Cytokine-cytokine receptor interaction
KO pathway
