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 system
BRITE hierarchy
Pathway map
ko04650 Natural killer cell mediated cytotoxicity
Ortholog table
Drug
Other DBs
Orthology
K07980 killer cell immunoglobulin-like receptor 3DL
K07981 killer cell immunoglobulin-like receptor 2DL1/2/3
K24232 killer cell immunoglobulin-like receptor 2DL5
K06541 killer cell lectin-like receptor subfamily C1
K06516 killer cell lectin-like receptor subfamily D member 1
K07293 tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48 ]
K06490 intercellular adhesion molecule 1
K06523 intercellular adhesion molecule 2
K05730 guanine nucleotide exchange factor VAV
K04392 Ras-related C3 botulinum toxin substrate 1
K07860 Ras-related C3 botulinum toxin substrate 2
K07861 Ras-related C3 botulinum toxin substrate 3
K03156 tumor necrosis factor superfamily, member 2
K05427 granulocyte-macrophage colony-stimulating factor
K07982 killer cell immunoglobulin-like receptor 2DS
K24233 killer cell lectin-like receptor subfamily C2/3
K06742 natural cytotoxicity triggering receptor 2
K07992 TYRO protein tyrosine kinase binding protein
K19251 Influenza A virus hemagglutinin
K06856 immunoglobulin heavy chain
K06463 low affinity immunoglobulin gamma Fc receptor III
K06741 natural cytotoxicity triggering receptor 1
K06743 natural cytotoxicity triggering receptor 3
K07983 high affinity immunoglobulin epsilon receptor subunit gamma
K06453 CD3Z antigen, zeta polypeptide
K07361 lymphocyte cytosolic protein 2
K07362 linker for activation of T cells family member 1
K26356 linker for activation of T-cells family member 2
K07984 SH3-domain binding protein 2
K00922 phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K02649 phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K06279 SHC-transforming protein 1
K17447 SHC-transforming protein 2
K17448 SHC-transforming protein 3
K17449 SHC-transforming protein 4
K04364 growth factor receptor-bound protein 2
K08845 A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04365 B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K07985 MHC class I-related protein
K06728 killer cell lectin-like receptor subfamily K member 1
K07988 hematopoietic cell signal transducer
K06582 natural killer cell receptor 2B4
K04348 serine/threonine-protein phosphatase 2B catalytic subunit [EC:3.1.3.16 ]
K06268 serine/threonine-protein phosphatase 2B regulatory subunit
K04446 nuclear factor of activated T-cells, cytoplasmic 1
K17332 nuclear factor of activated T-cells, cytoplasmic 2
K07989 SH2 domain-containing protein 1B
K07990 SH2 domain-containing protein 1A
K05132 interferon gamma receptor 1
K05133 interferon gamma receptor 2
K04721 tumor necrosis factor ligand superfamily member 10
K04722 tumor necrosis factor receptor superfamily member 10A/B
K04389 tumor necrosis factor ligand superfamily member 6
K04390 tumor necrosis factor receptor superfamily member 6
K04726 BH3 interacting domain death agonist
K24207 killer cell lectin-like receptor subfamily A member 1
K24208 killer cell lectin-like receptor subfamily A member 3
K24238 killer cell lectin-like receptor subfamily A member 7
K24240 killer cell lectin-like receptor subfamily A member 9
K23459 killer cell lectin-like receptor subfamily A member 4
K24239 killer cell lectin-like receptor subfamily A member 8
K07987 retinoic acid early transcript 1
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
ko04060 Cytokine-cytokine receptor interaction
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