Entry Name Natural killer cell mediated cytotoxicity - Peromyscus leucopus (white-footed mouse)
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 pleu04650 Natural killer cell mediated cytotoxicity
Other DBs Organism Peromyscus leucopus (white-footed mouse) [GN:
pleu ]
Gene 114680645 Rac3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861 ]
114681640 Hcst; hematopoietic cell signal transducer isoform X1 [KO:K07988 ]
114683255 Ppp3ca; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
114683897 Shc4; LOW QUALITY PROTEIN: SHC-transforming protein 4 [KO:K17449 ]
114684032 Pik3cd; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114684216 Vav2; guanine nucleotide exchange factor VAV2 isoform X4 [KO:K05730 ]
114684433 Nfatc2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332 ]
114685425 Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983 ]
114688966 Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X1 [KO:K02649 ]
114689925 Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453 ]
114689971 Faslg; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389 ]
114693559 Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922 ] [EC:2.7.1.153 ]
114693647 Lat2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356 ]
114694913 Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446 ]
114695335 Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922 ] [EC:2.7.1.153 ]
114697551 Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721 ]
114698437 Ifnar2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131 ]
114698768 Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348 ] [EC:3.1.3.16 ]
114699957 Vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730 ]
114700198 Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348 ] [EC:3.1.3.16 ]
114700306 Lat; linker for activation of T-cells family member 1 isoform X1 [KO:K07362 ]
114700391 Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427 ]
114701393 Klrk1; NKG2-D type II integral membrane protein isoform X1 [KO:K06728 ]
114703850 Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649 ]
114706924 Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649 ]
114707535 Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392 ]
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 pleu04060 Cytokine-cytokine receptor interaction
KO pathway
