Entry Name Natural killer cell mediated cytotoxicity
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 ko04650 Natural killer cell mediated cytotoxicity
Drug Other DBs Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01116 PLCG1; phosphatidylinositol phospholipase C, gamma-1 [EC:3.1.4.11 ]
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03156 TNF, TNFA; tumor necrosis factor superfamily, member 2
K04348 PPP3C, CNA; serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04389 TNFSF6, FASL, CD178; tumor necrosis factor ligand superfamily member 6
K04390 TNFRSF6, FAS, CD95; tumor necrosis factor receptor superfamily member 6
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04446 NFATC1, NFAT2, NFATC; nuclear factor of activated T-cells, cytoplasmic 1
K04721 TNFSF10, TRAIL, CD253; tumor necrosis factor ligand superfamily member 10
K04722 TNFRSF10A_B, TRAILR1_2, DR4_5, CD261_2; tumor necrosis factor receptor superfamily member 10A/B
K04726 BID; BH3 interacting domain death agonist
K05130 IFNAR1; interferon receptor 1
K05131 IFNAR2; interferon receptor 2
K05132 IFNGR1, CD119; interferon gamma receptor 1
K05133 IFNGR2; interferon gamma receptor 2
K05427 CSF2, GMCSF; granulocyte-macrophage colony-stimulating factor
K05697 PTPN6, SHP1; tyrosine-protein phosphatase non-receptor type 6 [EC:3.1.3.48 ]
K05718 ITGAL, CD11a; integrin alpha L
K05730 VAV; guanine nucleotide exchange factor VAV
K05856 LCK; lymphocyte cell-specific protein tyrosine kinase [EC:2.7.10.2 ]
K05859 PLCG2; phosphatidylinositol phospholipase C, gamma-2 [EC:3.1.4.11 ]
K06268 PPP3R, CNB; serine/threonine-protein phosphatase 2B regulatory subunit
K06279 SHC1; SHC-transforming protein 1
K06453 CD3Z, CD247; CD3Z antigen, zeta polypeptide
K06463 FCGR3, CD16; low affinity immunoglobulin gamma Fc receptor III
K06464 ITGB2, CD18; integrin beta 2
K06479 CD48, BCM1; CD48 antigen
K06490 ICAM1, CD54; intercellular adhesion molecule 1
K06516 KLRD1, CD94; killer cell lectin-like receptor subfamily D member 1
K06523 ICAM2, CD102; intercellular adhesion molecule 2
K06541 KLRC1, NKG2A; killer cell lectin-like receptor subfamily C1
K06582 CD244; natural killer cell receptor 2B4
K06728 KLRK1, CD314; killer cell lectin-like receptor subfamily K member 1
K06741 NCR1, CD335; natural cytotoxicity triggering receptor 1
K06742 NCR2, CD336; natural cytotoxicity triggering receptor 2
K06743 NCR3, CD337; natural cytotoxicity triggering receptor 3
K06856 IGH; immunoglobulin heavy chain
K07293 PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48 ]
K07361 LCP2; lymphocyte cytosolic protein 2
K07362 LAT; linker for activation of T cells family member 1
K07827 KRAS, KRAS2; GTPase KRas
K07860 RAC2; Ras-related C3 botulinum toxin substrate 2
K07861 RAC3; Ras-related C3 botulinum toxin substrate 3
K07983 FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma
K07984 SH3BP2; SH3-domain binding protein 2
K07985 MIC; MHC class I-related protein
K07986 ULBP; UL16 binding protein
K07987 RAET1; retinoic acid early transcript 1
K07988 HCST, DAP10; hematopoietic cell signal transducer
K07989 SH2D1B, EAT2; SH2 domain-containing protein 1B
K07990 SH2D1A, SAP; SH2 domain-containing protein 1A
K07992 TYROBP, DAP12; TYRO protein tyrosine kinase binding protein
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K17332 NFATC2, NFAT1, NFATP; nuclear factor of activated T-cells, cytoplasmic 2
K17447 SHC2; SHC-transforming protein 2
K17448 SHC3; SHC-transforming protein 3
K17449 SHC4; SHC-transforming protein 4
K19251 HA; Influenza A virus hemagglutinin
K24233 KLRC2_3, NKG2C_E; killer cell lectin-like receptor subfamily C2/3
K26356 LAT2, LAB; linker for activation of T-cells family member 2
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 ko04060 Cytokine-cytokine receptor interaction
