Entry Name Natural killer cell mediated cytotoxicity - Gracilinanus agilis (agile gracile opossum)
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 gas04650 Natural killer cell mediated cytotoxicity
Other DBs Organism Gracilinanus agilis (agile gracile opossum) [GN:
gas ]
Gene 123230879 LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362 ]
123231336 SHC3; LOW QUALITY PROTEIN: SHC-transforming protein 3 [KO:K17448 ]
123233411 TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722 ]
123233999 CD247; LOW QUALITY PROTEIN: T-cell surface glycoprotein CD3 zeta chain [KO:K06453 ]
123234292 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
123236876 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
123236954 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
123237139 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332 ]
123237207 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
123237416 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
123239917 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446 ]
123240288 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
123242322 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
123242831 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
123245896 FASLG; LOW QUALITY PROTEIN: tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
123247043 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983 ]
123247605 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
123252235 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
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 gas04060 Cytokine-cytokine receptor interaction
KO pathway
