KEGG   PATHWAY: tod04650
Entry
tod04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Talpa occidentalis (Iberian mole)
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
tod04650  Natural killer cell mediated cytotoxicity
tod04650

Other DBs
GO: 0042267
Organism
Talpa occidentalis (Iberian mole) [GN:tod]
Gene
119258452  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119250939  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119237512  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246991  NKG2-C type II integral membrane protein-like [KO:K06541]
119246992  NKG2-C type II integral membrane protein-like [KO:K06541]
119246993  NKG2-C type II integral membrane protein-like [KO:K06541]
119246994  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246995  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246996  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246997  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246998  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119246999  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247000  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247002  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247004  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247005  NKG2-C type II integral membrane protein-like [KO:K06541]
119247006  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247007  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119240139  NKG2-F type II integral membrane protein-like [KO:K06541]
119247716  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247719  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
119247720  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
119248342  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
119248345  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
119237836  natural killer cells antigen CD94-like [KO:K06516]
119254057  natural killer cells antigen CD94-like [KO:K06516]
119247009  natural killer cells antigen CD94-like [KO:K06516]
119247011  natural killer cells antigen CD94-like [KO:K06516]
119247012  natural killer cells antigen CD94-like [KO:K06516]
119247013  natural killer cells antigen CD94-like [KO:K06516]
119247015  natural killer cells antigen CD94-like [KO:K06516]
119247016  natural killer cells antigen CD94-like [KO:K06516]
119247017  natural killer cells antigen CD94-like [KO:K06516]
119247020  natural killer cells antigen CD94-like [KO:K06516]
119247021  natural killer cells antigen CD94-like [KO:K06516]
119247023  natural killer cells antigen CD94-like [KO:K06516]
119248350  natural killer cells antigen CD94-like [KO:K06516]
119248351  natural killer cells antigen CD94-like [KO:K06516]
119247764  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
119244965  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
119240938  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
119231016  ICAM2; intercellular adhesion molecule 2 isoform X1 [KO:K06523]
119233334  LOW QUALITY PROTEIN: integrin alpha-L-like [KO:K05718]
119241739  ITGAL; integrin alpha-L [KO:K05718]
119257148  ITGB2; LOW QUALITY PROTEIN: integrin beta-2 [KO:K06464]
119258011  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
119235099  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
119231223  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
119240642  VAV1; proto-oncogene vav [KO:K05730]
119241672  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
119248240  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
119230847  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
119255656  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
119238768  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
119240577  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
119234388  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
119241775  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
119253235  TNF; tumor necrosis factor isoform X1 [KO:K03156]
119242737  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
119248294  IFNG; interferon gamma [KO:K04687]
119250245  TYROBP; TYRO protein tyrosine kinase-binding protein [KO:K07992]
119235229  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
119240091  low affinity immunoglobulin gamma Fc region receptor III-B-like isoform X1 [KO:K06463]
119249742  natural cytotoxicity triggering receptor 1-like isoform X1 [KO:K06741]
119251347  NCR3; LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 3 [KO:K06743]
119241376  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
119242275  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
119259916  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
119232025  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
119235546  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
119240182  LAT; LOW QUALITY PROTEIN: linker for activation of T-cells family member 1 [KO:K07362]
119242322  LAT2; linker for activation of T-cells family member 2 isoform X3 [KO:K26356]
119235450  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
119249121  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
119260943  SH3BP2; SH3 domain-binding protein 2 isoform X1 [KO:K07984]
119257726  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
119236721  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
119257304  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
119237093  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
119260810  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
119241117  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
119252791  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
119235491  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
119240463  SHC2; SHC-transforming protein 2 [KO:K17447]
119231849  SHC3; SHC-transforming protein 3 [KO:K17448]
119238599  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
119232938  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
119259378  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
119239071  SOS2; son of sevenless homolog 2 [KO:K03099]
119249824  HRAS; GTPase HRas isoform X1 [KO:K02833]
119247626  KRAS; GTPase KRas isoform X1 [KO:K07827]
119236713  NRAS; GTPase NRas [KO:K07828]
119246187  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
119247810  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
119255730  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
119252130  MHC class I polypeptide-related sequence B-like [KO:K07985]
119252131  MHC class I polypeptide-related sequence A-like [KO:K07985]
119252134  MHC class I polypeptide-related sequence B-like [KO:K07985]
119252135  MHC class I polypeptide-related sequence A-like [KO:K07985]
119253223  MHC class I polypeptide-related sequence B-like isoform X1 [KO:K07985]
119251547  UL16-binding protein 1-like isoform X1 [KO:K07986]
119251548  UL16-binding protein 1-like [KO:K07986]
119251554  UL16-binding protein 1-like [KO:K07986]
119252974  UL16-binding protein 1-like isoform X2 [KO:K07986]
119253495  uncharacterized protein LOC119253495 [KO:K07986]
119256653  UL16-binding protein 1-like [KO:K07986]
119256655  UL16-binding protein 1-like [KO:K07986]
119247008  KLRK1; NKG2-D type II integral membrane protein [KO:K06728]
119242292  LOW QUALITY PROTEIN: CD48 antigen-like [KO:K06479]
119240098  CD48 antigen [KO:K06479]
119242288  CD244; natural killer cell receptor 2B4 [KO:K06582]
119234581  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119234881  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
119243687  PPP3CA; protein phosphatase 3 catalytic subunit alpha [KO:K04348] [EC:3.1.3.16]
119231203  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
119259019  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
119242960  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
119236570  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
119231758  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
119241818  PRKCB; protein kinase C beta type isoform X2 [KO:K19662] [EC:2.7.11.13]
119249714  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
119240087  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
119245913  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
119252911  IFNGR1; interferon gamma receptor 1 [KO:K05132]
119257088  IFNGR2; interferon gamma receptor 2 [KO:K05133]
119232539  interferon alpha-6-like [KO:K05414]
119231101  IFNB1; interferon beta [KO:K05415]
119257231  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
119257233  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
119257290  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
119233979  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A isoform X1 [KO:K04722]
119240071  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
119233895  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
119238086  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
119238241  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
119238975  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
119239511  mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
119234362  perforin-1-like [KO:K07818]
119233556  perforin-1-like [KO:K07818]
119233901  perforin-1-like [KO:K07818]
119233902  perforin-1-like [KO:K07818]
119234298  PRF1; perforin-1 [KO:K07818]
119257947  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
119247866  BID; BH3-interacting domain death agonist [KO:K04726]
119252971  retinoic acid early transcript 1E-like [KO:K07987]
119252972  retinoic acid early transcript 1E-like [KO:K07987]
119252975  retinoic acid early transcript 1E-like [KO:K07987]
119252976  LOW QUALITY PROTEIN: retinoic acid early transcript 1E-like [KO:K07987]
119256654  retinoic acid early transcript 1E-like [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
tod04010  MAPK signaling pathway
tod04020  Calcium signaling pathway
tod04060  Cytokine-cytokine receptor interaction
tod04210  Apoptosis
tod04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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