KEGG   PATHWAY: btax04650
Entry
btax04650                   Pathway                                
Name
Natural killer cell mediated cytotoxicity - Budorcas taxicolor (takin)
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
btax04650  Natural killer cell mediated cytotoxicity
btax04650

Other DBs
GO: 0042267
Organism
Budorcas taxicolor (takin) [GN:btax]
Gene
128063231  LOW QUALITY PROTEIN: putative killer cell immunoglobulin-like receptor like protein KIR3DP1 [KO:K07980]
128063487  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
128063513  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
128063578  putative killer cell immunoglobulin-like receptor like protein KIR3DP1 [KO:K07980]
128063589  putative killer cell immunoglobulin-like receptor like protein KIR3DP1 [KO:K07980]
128064081  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
128047924  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
128047925  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
128048398  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
128048445  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
128048624  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
128048234  natural killer cells antigen CD94-like [KO:K06516]
128048235  natural killer cells antigen CD94-like [KO:K06516]
128047743  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
128062064  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
128061515  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
128050899  intercellular adhesion molecule 1 [KO:K06490]
128051541  LOW QUALITY PROTEIN: intercellular adhesion molecule 1-like [KO:K06490]
128065007  intercellular adhesion molecule 2-like isoform X1 [KO:K06523]
128065008  intercellular adhesion molecule 2-like [KO:K06523]
128065009  intercellular adhesion molecule 2-like [KO:K06523]
128065010  intercellular adhesion molecule 2-like [KO:K06523]
128070817  ITGAL; integrin alpha-L [KO:K05718]
128047159  ITGB2; integrin beta-2 [KO:K06464]
128052409  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
128050828  VAV1; proto-oncogene vav [KO:K05730]
128044678  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
128055501  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
128043471  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
128047644  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
128065663  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
128068496  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
128054045  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
128050664  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
128043958  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
128062160  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
128056772  TNF; tumor necrosis factor [KO:K03156]
128051607  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
128048506  IFNG; interferon gamma [KO:K04687]
128063695  TYROBP; TYRO protein tyrosine kinase-binding protein [KO:K07992]
128062412  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
128044373  low affinity immunoglobulin gamma Fc region receptor III-A-like [KO:K06463]
128062787  natural cytotoxicity triggering receptor 1 [KO:K06741]
128056861  NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]
128045341  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
128045120  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
128056450  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
128052376  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
128066168  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
128043776  LAT; linker for activation of T-cells family member 1 [KO:K07362]
128043546  LAT2; linker for activation of T-cells family member 2 [KO:K26356]
128058189  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
128063111  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
128049599  SH3BP2; SH3 domain-binding protein 2 isoform X1 [KO:K07984]
128045803  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
128061813  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
128068699  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
128050540  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
128044474  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
128066235  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
128053552  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
128044445  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
128051196  SHC2; SHC-transforming protein 2 [KO:K17447]
128052614  SHC3; SHC-transforming protein 3 [KO:K17448]
128054009  SHC4; SHC-transforming protein 4 [KO:K17449]
128064562  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
128053892  SOS2; son of sevenless homolog 2 [KO:K03099]
128055374  SOS1; son of sevenless homolog 1 [KO:K03099]
128068689  HRAS; GTPase HRas isoform X1 [KO:K02833]
128047937  KRAS; GTPase KRas [KO:K07827]
128044537  NRAS; GTPase NRas [KO:K07828]
128070468  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
128046969  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
128043403  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
128055284  MHC class I polypeptide-related sequence B-like [KO:K07985]
128053163  LOW QUALITY PROTEIN: UL16-binding protein 3-like [KO:K07986]
128053165  UL16-binding protein 2-like [KO:K07986]
128053167  UL16-binding protein 1-like [KO:K07986]
128053168  LOW QUALITY PROTEIN: UL16-binding protein 2-like [KO:K07986]
128053436  UL16-binding protein 3-like [KO:K07986]
128053437  UL16-binding protein 1-like [KO:K07986]
128053438  UL16-binding protein 2-like [KO:K07986]
128053439  UL16-binding protein 1-like [KO:K07986]
128053441  UL16-binding protein 1-like [KO:K07986]
128053444  LOW QUALITY PROTEIN: UL16-binding protein 3-like [KO:K07986]
128048821  KLRK1; NKG2-D type II integral membrane protein [KO:K06728]
128063881  HCST; hematopoietic cell signal transducer [KO:K07988]
128044841  CD48 antigen-like [KO:K06479]
128045279  CD48 antigen-like [KO:K06479]
128045280  CD48 antigen-like [KO:K06479]
128045474  CD244; natural killer cell receptor 2B4 [KO:K06582]
128052144  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
128047312  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform [KO:K04348] [EC:3.1.3.16]
128049447  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
128052606  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
128055318  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
128067290  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
128058335  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
128065393  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
128066420  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
128063096  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
128045750  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
128070460  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
128053263  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
128047334  IFNGR2; interferon gamma receptor 2 [KO:K05133]
128052429  interferon alpha-H-like [KO:K05414]
128052430  interferon alpha-H-like [KO:K05414]
128052431  interferon alpha-H [KO:K05414]
128052432  interferon alpha-1-like [KO:K05414]
128052433  interferon alpha-H-like [KO:K05414]
128052459  interferon alpha-H-like [KO:K05414]
128052476  interferon alpha-H-like [KO:K05414]
128052682  LOW QUALITY PROTEIN: interferon alpha-3-like [KO:K05414]
128052694  interferon alpha-H-like [KO:K05414]
128052696  interferon alpha-H-like [KO:K05414]
128052697  interferon alpha-1-like [KO:K05414]
128052706  LOW QUALITY PROTEIN: interferon alpha-2-like [KO:K05414]
128052625  interferon beta-2-like [KO:K05415]
128052626  interferon beta-2-like [KO:K05415]
128052627  interferon beta-2-like [KO:K05415]
128052628  interferon beta-2 [KO:K05415]
128052635  interferon beta-2-like [KO:K05415]
128052636  interferon beta-2-like [KO:K05415]
128052637  interferon beta-2-like [KO:K05415]
128052638  interferon beta-2-like [KO:K05415]
128052639  interferon beta-2-like [KO:K05415]
128052640  interferon beta-2-like [KO:K05415]
128052652  interferon beta-2-like [KO:K05415]
128044048  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
128055500  interferon alpha/beta receptor 2 [KO:K05131]
128055119  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
128052079  tumor necrosis factor receptor superfamily member 10C-like [KO:K04722]
128052097  tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]
128052227  tumor necrosis factor receptor superfamily member 10C-like isoform X1 [KO:K04722]
128061812  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
128067871  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
128066475  mast cell protease 1A [KO:K01353] [EC:3.4.21.79]
128066549  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128066641  mast cell protease 3 [KO:K01353] [EC:3.4.21.79]
128066644  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
128067007  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128067008  granzyme B-like [KO:K01353] [EC:3.4.21.79]
128048835  PRF1; perforin-1 [KO:K07818]
128068336  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
128047923  BID; BH3-interacting domain death agonist [KO:K04726]
128053442  retinoic acid early transcript 1E-like [KO:K07987]
128053443  retinoic acid early transcript 1E-like [KO:K07987]
128053446  RAET1E; retinoic acid early transcript 1E [KO:K07987]
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
btax04010  MAPK signaling pathway
btax04020  Calcium signaling pathway
btax04060  Cytokine-cytokine receptor interaction
btax04210  Apoptosis
btax04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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