KEGG   PATHWAY: fca04650
Entry
fca04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Felis catus (domestic cat)
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
Pathway map
fca04650  Natural killer cell mediated cytotoxicity
fca04650

Other DBs
GO: 0042267
Organism
Felis catus (domestic cat) [GN:fca]
Gene
100113473  PRF1; perforin-1 precursor [KO:K07818]
100127106  GZMB; granzyme B(G,H) [KO:K01353] [EC:3.4.21.79]
100174789  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
100271864  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X3 [KO:K02649]
100502578  BID; BH3-interacting domain death agonist [KO:K04726]
101080496  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
101080520  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101080604  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
101080675  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X2 [KO:K05859] [EC:3.1.4.11]
101081371  [KO:K05414]
101081387  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X3 [KO:K04368] [EC:2.7.12.2]
101082196  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101082222  [KO:K07293] [EC:3.1.3.48]
101082237  [KO:K07987]
101082964  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
101083489  SHC2; SHC-transforming protein 2 isoform X2 [KO:K17447]
101083998  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
101085500  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
101085720  FYN; LOW QUALITY PROTEIN: tyrosine-protein kinase Fyn [KO:K05703] [EC:2.7.10.2]
101085940  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
101086264  VAV2; guanine nucleotide exchange factor VAV2 isoform X7 [KO:K05730]
101086433  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101086731  KLRD1; natural killer cells antigen CD94 isoform X1 [KO:K06516]
101086811  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101086926  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101086984  [KO:K06728]
101087013  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
101087073  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
101087171  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
101087258  ITGB2; integrin beta-2 [KO:K06464]
101087417  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
101087614  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101087958  MAPK3; mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
101088440  [KO:K05414]
101088847  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
101088970  PRKCB; protein kinase C beta type isoform X3 [KO:K19662] [EC:2.7.11.13]
101089073  CD244; natural killer cell receptor 2B4 isoform X1 [KO:K06582]
101089236  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101089421  ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]
101089831  CD48; CD48 antigen isoform X2 [KO:K06479]
101089839  ARAF; serine/threonine-protein kinase A-Raf isoform X2 [KO:K08845] [EC:2.7.11.1]
101090285  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
101090344  PPP3R1; calcineurin subunit B type 1 isoform X4 [KO:K06268]
101090864  NCR2; natural cytotoxicity triggering receptor 2 [KO:K06742]
101091691  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
101091892  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
101092286  IFNGR2; interferon gamma receptor 2 [KO:K05133]
101092346  BRAF; serine/threonine-protein kinase B-raf isoform X5 [KO:K04365] [EC:2.7.11.1]
101092535  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
101092911  SHC1; SHC-transforming protein 1 isoform X3 [KO:K06279]
101092925  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101093097  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
101093286  [KO:K02649]
101093319  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
101093586  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101094153  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
101094274  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
101094307  [KO:K06741]
101095723  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
101095865  SHC3; SHC-transforming protein 3 [KO:K17448]
101096047  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101096744  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101096877  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101097059  ZAP70; tyrosine-protein kinase ZAP-70 isoform X2 [KO:K07360] [EC:2.7.10.2]
101097144  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101097212  VAV1; proto-oncogene vav isoform X3 [KO:K05730]
101097239  SH3BP2; SH3 domain-binding protein 2 isoform X2 [KO:K07984]
101097286  HCST; hematopoietic cell signal transducer isoform X1 [KO:K07988]
101097413  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101097765  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
101098351  LAT2; linker for activation of T-cells family member 2 isoform X2 [KO:K26356]
101098805  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
101098862  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
101098907  ICAM2; intercellular adhesion molecule 2 [KO:K06523]
101099050  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
101099215  [KO:K01353] [EC:3.4.21.79]
101099916  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
101100052  NCR3; natural cytotoxicity triggering receptor 3 isoform X1 [KO:K06743]
101100281  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101100397  [KO:K06541]
101100648  [KO:K06541]
101100897  [KO:K06541]
101101259  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
101101277  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X3 [KO:K04392]
102899212  [KO:K07986]
105260590  [KO:K07986]
105261012  [KO:K04722]
111557596  [KO:K05414]
111561475  [KO:K06541]
123381775  [KO:K05414]
123386529  [KO:K06541]
123386856  [KO:K06541]
493648  IFNA8; interferon alpha-8 precursor [KO:K05414]
493653  IFNA7; interferon alpha precursor [KO:K05414]
493677  FCGR3A; low affinity immunoglobulin gamma Fc region receptor III-A precursor [KO:K06463]
493755  TNF; tumor necrosis factor precursor [KO:K03156]
493840  IFNA5; interferon alpha-5 [KO:K05414]
493849  IFNB1; interferon beta precursor [KO:K05415]
493881  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
493932  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
493945  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
493965  IFNG; interferon gamma precursor [KO:K04687]
751103  HRAS; GTPase HRas isoform X1 [KO:K02833]
751104  KRAS; GTPase KRas isoform X2 [KO:K07827]
751105  NRAS; GTPase NRas [KO:K07828]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C01245  D-myo-Inositol 1,4,5-trisphosphate
C05981  Phosphatidylinositol-3,4,5-trisphosphate
Reference
PMID:15607802
  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)
DOI:10.1016/j.molimm.2004.07.030
Reference
PMID:16109839
  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)
DOI:10.1124/pr.57.3.5
Reference
PMID:15567854
  Authors
Vivier E, Nunes JA, Vely F.
  Title
Natural killer cell signaling pathways.
  Journal
Science 306:1517-9 (2004)
DOI:10.1126/science.1103478
Reference
PMID:12205470
  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)
DOI:10.1038/ni0902-807
Reference
PMID:11062493
  Authors
Perussia B.
  Title
Signaling for cytotoxicity.
  Journal
Nat Immunol 1:372-4 (2000)
DOI:10.1038/80808
Reference
PMID:15607806
  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)
DOI:10.1016/j.molimm.2004.07.034
Reference
PMID:11895890
  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
PMID:12530970
  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)
DOI:10.1016/S1074-7613(02)00502-2
Reference
PMID:16177799
  Authors
Colonna M.
  Title
Fine-tuning NK cell responses: it's a family affair.
  Journal
Nat Immunol 6:961-2 (2005)
DOI:10.1038/ni1005-961
Reference
PMID:8942070
  Authors
Bonnema JD, Leibson PJ.
  Title
Signal transduction during NK cell activation.
  Journal
Chem Immunol 64:28-43 (1996)
Reference
PMID:16002670
  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)
DOI:10.4049/jimmunol.175.2.749
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)
DOI:10.1146/annurev.immunol.15.1.707
Reference
PMID:14710949
  Authors
Wu J, Lanier LL.
  Title
Natural killer cells and cancer.
  Journal
Adv Cancer Res 90:127-56 (2003)
DOI:10.1016/S0065-230X(03)90004-2
Reference
PMID:11905813
  Authors
Cerwenka A, Lanier LL.
  Title
Natural killer cells, viruses and cancer.
  Journal
Nat Rev Immunol 1:41-9 (2001)
DOI:10.1038/35095564
Reference
PMID:11836514
  Authors
Blott EJ, Griffiths GM.
  Title
Secretory lysosomes.
  Journal
Nat Rev Mol Cell Biol 3:122-31 (2002)
DOI:10.1038/nrm732
Reference
PMID:12766758
  Authors
Lieberman J.
  Title
The ABCs of granule-mediated cytotoxicity: new weapons in the arsenal.
  Journal
Nat Rev Immunol 3:361-70 (2003)
DOI:10.1038/nri1083
Reference
PMID:12752668
  Authors
Lord SJ, Rajotte RV, Korbutt GS, Bleackley RC.
  Title
Granzyme B: a natural born killer.
  Journal
Immunol Rev 193:31-8 (2003)
DOI:10.1034/j.1600-065X.2003.00044.x
Reference
PMID:15618404
  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)
DOI:10.1073/pnas.0405737102
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
PMID:11390470
  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)
DOI:10.4049/jimmunol.166.12.7219
Related
pathway
fca04010  MAPK signaling pathway
fca04020  Calcium signaling pathway
fca04060  Cytokine-cytokine receptor interaction
fca04210  Apoptosis
fca04630  JAK-STAT signaling pathway
KO pathway
ko04650   

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