Entry
Name
Natural killer cell mediated cytotoxicity - Hyaena hyaena (striped hyena)
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 system
BRITE hierarchy
Pathway map
hhv04650 Natural killer cell mediated cytotoxicity
Ortholog table
Other DBs
Organism
Hyaena hyaena (striped hyena) [GN:
hhv ]
Gene
120224084 NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541 ]
120247312 VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730 ]
120227958 RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
120228188 RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
120245487 CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
120243469 TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992 ]
120241040 FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A isoform X1 [KO:K06463 ]
120239734 NCR1; natural cytotoxicity triggering receptor 1 isoform X1 [KO:K06741 ]
120241422 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983 ]
120238260 CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
120242177 LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
120247357 LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356 ]
120228585 PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116 ] [EC:3.1.4.11 ]
120233608 PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922 ] [EC:2.7.1.153 ]
120220979 PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
120246696 PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
120219997 PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
120239233 PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649 ]
120247089 phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649 ]
120225617 PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348 ] [EC:3.1.3.16 ]
120233735 PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
120239494 PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
120240942 NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
120230427 NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
120234588 TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
120233928 tumor necrosis factor receptor superfamily member 25-like isoform X1 [KO:K04722 ]
120224200 FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389 ]
120223778 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 pathway
hhv04060 Cytokine-cytokine receptor interaction
KO pathway
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