KEGG   PATHWAY: mmu04650Help
Entry
mmu04650                    Pathway                                

Name
Natural killer cell mediated cytotoxicity - Mus musculus (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 system
BRITE hierarchy
Pathway map
Natural killer cell mediated cytotoxicity
mmu04650

All organismsOrtholog table
Other DBs
BSID: 
GO: 
Organism
Mus musculus (mouse) [GN:mmu]
Gene
15040  
H2-T23; histocompatibility 2, T region locus 23 [KO:K06751]
14964  
H2-D1; histocompatibility 2, D region locus 1 [KO:K06751]
14972  
H2-K1; histocompatibility 2, K1, K region [KO:K06751]
16641  
Klrc1; killer cell lectin-like receptor subfamily C, member 1 [KO:K06541]
16642  
Klrc2; killer cell lectin-like receptor subfamily C, member 2 [KO:K06541]
16643  
Klrd1; killer cell lectin-like receptor, subfamily D, member 1 [KO:K06516]
15170  
Ptpn6; protein tyrosine phosphatase, non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
19247  
Ptpn11; protein tyrosine phosphatase, non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
15894  
Icam1; intercellular adhesion molecule 1 [KO:K06490]
15896  
Icam2; intercellular adhesion molecule 2 [KO:K06523]
16408  
Itgal; integrin alpha L [KO:K05718]
16414  
Itgb2; integrin beta 2 [KO:K06464]
16415  
Itgb2l; integrin beta 2-like [KO:K06464]
19229  
Ptk2b; PTK2 protein tyrosine kinase 2 beta [KO:K05871] [EC:2.7.10.2]
22324  
Vav1; vav 1 oncogene [KO:K05730]
22325  
Vav2; vav 2 oncogene [KO:K05730]
57257  
Vav3; vav 3 oncogene [KO:K05730]
19353  
Rac1; RAS-related C3 botulinum substrate 1 [KO:K04392]
19354  
Rac2; RAS-related C3 botulinum substrate 2 [KO:K07860]
170758  
Rac3; RAS-related C3 botulinum substrate 3 [KO:K07861]
18479  
Pak1; p21 protein (Cdc42/Rac)-activated kinase 1 [KO:K04409] [EC:2.7.11.1]
26395  
Map2k1; mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
26396  
Map2k2; mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
26413  
Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
26417  
Mapk3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
21926  
Tnf; tumor necrosis factor [KO:K03156]
12981  
Csf2; colony stimulating factor 2 (granulocyte-macrophage) [KO:K05427]
15978  
Ifng; interferon gamma [KO:K04687]
22177  
Tyrobp; TYRO protein tyrosine kinase binding protein [KO:K07992]
16818  
Lck; lymphocyte protein tyrosine kinase [KO:K05856] [EC:2.7.10.2]
IgH; uncharacterized LOC102642252 [KO:K06856]
IgH; Ig heavy chain Mem5-like [KO:K06856]
246256  
Fcgr4; Fc receptor, IgG, low affinity IV [KO:K06463]
17086  
Ncr1; natural cytotoxicity triggering receptor 1 [KO:K06741]
14127  
Fcer1g; Fc receptor, IgE, high affinity I, gamma polypeptide [KO:K07983]
12503  
Cd247; CD247 antigen [KO:K06453]
22637  
Zap70; zeta-chain (TCR) associated protein kinase [KO:K07360] [EC:2.7.10.2]
20963  
Syk; spleen tyrosine kinase [KO:K05855] [EC:2.7.10.2]
16822  
Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
16797  
Lat; linker for activation of T cells [KO:K07362]
18803  
Plcg1; phospholipase C, gamma 1 [KO:K01116] [EC:3.1.4.11]
234779  
Plcg2; phospholipase C, gamma 2 [KO:K05859] [EC:3.1.4.11]
24055  
Sh3bp2; SH3-domain binding protein 2 [KO:K07984]
30955  
Pik3cg; phosphoinositide-3-kinase, catalytic, gamma polypeptide [KO:K00922] [EC:2.7.1.153]
18706  
Pik3ca; phosphatidylinositol 3-kinase, catalytic, alpha polypeptide [KO:K00922] [EC:2.7.1.153]
18707  
Pik3cd; phosphatidylinositol 3-kinase catalytic delta polypeptide [KO:K00922] [EC:2.7.1.153]
74769  
Pik3cb; phosphatidylinositol 3-kinase, catalytic, beta polypeptide [KO:K00922] [EC:2.7.1.153]
18709  
Pik3r2; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 2 (p85 beta) [KO:K02649]
18708  
Pik3r1; phosphatidylinositol 3-kinase, regulatory subunit, polypeptide 1 (p85 alpha) [KO:K02649]
320207  
Pik3r5; phosphoinositide-3-kinase, regulatory subunit 5, p101 [KO:K02649]
18710  
Pik3r3; phosphatidylinositol 3 kinase, regulatory subunit, polypeptide 3 (p55) [KO:K02649]
14360  
Fyn; Fyn proto-oncogene [KO:K05703] [EC:2.7.10.2]
20416  
Shc1; src homology 2 domain-containing transforming protein C1 [KO:K06279]
216148  
Shc2; SHC (Src homology 2 domain containing) transforming protein 2 [KO:K17447]
20418  
Shc3; src homology 2 domain-containing transforming protein C3 [KO:K17448]
271849  
Shc4; SHC (Src homology 2 domain containing) family, member 4 [KO:K17449]
14784  
Grb2; growth factor receptor bound protein 2 [KO:K04364]
20662  
Sos1; son of sevenless homolog 1 (Drosophila) [KO:K03099]
20663  
Sos2; son of sevenless homolog 2 (Drosophila) [KO:K03099]
15461  
Hras; Harvey rat sarcoma virus oncogene [KO:K02833]
16653  
Kras; Kirsten rat sarcoma viral oncogene homolog [KO:K07827]
18176  
Nras; neuroblastoma ras oncogene [KO:K07828]
11836  
Araf; Araf proto-oncogene, serine/threonine kinase [KO:K08845] [EC:2.7.11.1]
109880  
Braf; Braf transforming gene [KO:K04365] [EC:2.7.11.1]
110157  
Raf1; v-raf-leukemia viral oncogene 1 [KO:K04366] [EC:2.7.11.1]
19368  
Raet1a; retinoic acid early transcript 1, alpha [KO:K07987]
19369  
Raet1b; retinoic acid early transcript beta [KO:K07987]
19370  
Raet1c; retinoic acid early transcript gamma [KO:K07987]
56554  
Raet1d; retinoic acid early transcript delta [KO:K07987]
379043  
Raet1e; retinoic acid early transcript 1E [KO:K07987]
27007  
Klrk1; killer cell lectin-like receptor subfamily K, member 1 [KO:K06728]
23900  
Hcst; hematopoietic cell signal transducer [KO:K07988]
12506  
Cd48; CD48 antigen [KO:K06479]
18106  
Cd244; CD244 natural killer cell receptor 2B4 [KO:K06582]
19057  
Ppp3cc; protein phosphatase 3, catalytic subunit, gamma isoform [KO:K04348] [EC:3.1.3.16]
19055  
Ppp3ca; protein phosphatase 3, catalytic subunit, alpha isoform [KO:K04348] [EC:3.1.3.16]
19056  
Ppp3cb; protein phosphatase 3, catalytic subunit, beta isoform [KO:K04348] [EC:3.1.3.16]
19058  
Ppp3r1; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type I) [KO:K06268]
19059  
Ppp3r2; protein phosphatase 3, regulatory subunit B, alpha isoform (calcineurin B, type II) [KO:K06268]
18018  
Nfatc1; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 1 [KO:K04446]
18019  
Nfatc2; nuclear factor of activated T cells, cytoplasmic, calcineurin dependent 2 [KO:K17332]
18750  
Prkca; protein kinase C, alpha [KO:K02677] [EC:2.7.11.13]
18751  
Prkcb; protein kinase C, beta [KO:K19662] [EC:2.7.11.13]
18752  
Prkcg; protein kinase C, gamma [KO:K19663] [EC:2.7.11.13]
26904  
Sh2d1b1; SH2 domain containing 1B1 [KO:K07989]
20400  
Sh2d1a; SH2 domain containing 1A [KO:K07990]
15979  
Ifngr1; interferon gamma receptor 1 [KO:K05132]
15980  
Ifngr2; interferon gamma receptor 2 [KO:K05133]
15962  
Ifna1; interferon alpha 1 [KO:K05414]
15965  
Ifna2; interferon alpha 2 [KO:K05414]
15967  
Ifna4; interferon alpha 4 [KO:K05414]
15968  
Ifna5; interferon alpha 5 [KO:K05414]
15969  
Ifna6; interferon alpha 6 [KO:K05414]
15970  
Ifna7; interferon alpha 7 [KO:K05414]
15972  
Ifna9; interferon alpha 9 [KO:K05414]
15964  
Ifna11; interferon alpha 11 [KO:K05414]
242519  
Ifna12; interferon alpha 12 [KO:K05414]
230396  
Ifna13; interferon alpha 13 [KO:K05414]
404549  
Ifna14; interferon alpha 14 [KO:K05414]
15974  
Ifnab; interferon alpha B [KO:K05414]
242517  
Ifna15; interferon alpha 15 [KO:K05414]
15977  
Ifnb1; interferon beta 1, fibroblast [KO:K05415]
15975  
Ifnar1; interferon (alpha and beta) receptor 1 [KO:K05130]
15976  
Ifnar2; interferon (alpha and beta) receptor 2 [KO:K05131]
22035  
Tnfsf10; tumor necrosis factor (ligand) superfamily, member 10 [KO:K04721]
21933  
Tnfrsf10b; tumor necrosis factor receptor superfamily, member 10b [KO:K04722]
14103  
Fasl; Fas ligand (TNF superfamily, member 6) [KO:K04389]
14102  
Fas; Fas (TNF receptor superfamily member 6) [KO:K04390]
14939  
Gzmb; granzyme B [KO:K01353] [EC:3.4.21.79]
18646  
Prf1; perforin 1 (pore forming protein) [KO:K07818]
12367  
Casp3; caspase 3 [KO:K02187] [EC:3.4.22.56]
12122  
Bid; BH3 interacting domain death agonist [KO:K04726]
15101  
H60a; histocompatibility 60a
16627  
Klra1; killer cell lectin-like receptor, subfamily A, member 1
16634  
Klra3; killer cell lectin-like receptor, subfamily A, member 3
16635  
Klra4; killer cell lectin-like receptor, subfamily A, member 4
16638  
Klra7; killer cell lectin-like receptor, subfamily A, member 7
16639  
Klra8; killer cell lectin-like receptor, subfamily A, member 8
16640  
Klra9; killer cell lectin-like receptor subfamily A, member 9
17059  
Klrb1c; killer cell lectin-like receptor subfamily B member 1C [KO:K06543]
77777  
Ulbp1; UL16 binding protein 1
Compound
C00076  
Calcium cation
C00165  
Diacylglycerol
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
Mol Immunol 42:477-84 (2005)
Reference
  Authors
Maghazachi AA.
  Title
Insights into seven and single transmembrane-spanning domain receptors and their signaling pathways in human natural killer cells.
  Journal
Pharmacol Rev 57:339-57 (2005)
Reference
  Authors
Vivier E, Nunes JA, Vely F.
  Title
Natural killer cell signaling pathways.
  Journal
Science 306:1517-9 (2004)
Reference
  Authors
Colucci F, Di Santo JP, Leibson PJ.
  Title
Natural killer cell activation in mice and men: different triggers for similar weapons?
  Journal
Nat Immunol 3:807-13 (2002)
Reference
  Authors
Perussia B.
  Title
Signaling for cytotoxicity.
  Journal
Nat Immunol 1:372-4 (2000)
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
Mol Immunol 42:501-10 (2005)
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
Immunity 18:1-6 (2003)
Reference
  Authors
Colonna M.
  Title
Fine-tuning NK cell responses: it's a family affair.
  Journal
Nat Immunol 6:961-2 (2005)
Reference
PMID:8942070
  Authors
Bonnema JD, Leibson PJ.
  Title
Signal transduction during NK cell activation.
  Journal
Chem Immunol 64:28-43 (1996)
Reference
(Japanese)
  Authors
Satoh T, Arase H.
  Title
[Recognition of virus infected cells by NK cell receptor.] (In Japanese)
  Journal
Experimental Medicine 23(17):2685-2691 (2005)
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
J Immunol 175:749-54 (2005)
Reference
PMID:9143705
  Authors
Rao A, Luo C, Hogan PG.
  Title
Transcription factors of the NFAT family: regulation and function.
  Journal
Annu Rev Immunol 15:707-47 (1997)
Reference
  Authors
Wu J, Lanier LL.
  Title
Natural killer cells and cancer.
  Journal
Adv Cancer Res 90:127-56 (2003)
Reference
  Authors
Cerwenka A, Lanier LL.
  Title
Natural killer cells, viruses and cancer.
  Journal
Nat Rev Immunol 1:41-9 (2001)
Reference
  Authors
Blott EJ, Griffiths GM.
  Title
Secretory lysosomes.
  Journal
Nat Rev Mol Cell Biol 3:122-31 (2002)
Reference
  Authors
Lieberman J.
  Title
The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal.
  Journal
Nat Rev Immunol 3:361-70 (2003)
Reference
  Authors
Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
  Title
Granzyme B: a natural born killer.
  Journal
Immunol Rev 193:31-8 (2003)
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
Proc Natl Acad Sci U S A 102:123-7 (2005)
Reference
PMID:9862693
  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
J Immunol 166:7219-28 (2001)
KO pathway
 

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