KEGG   PATHWAY: oor04650
Entry
oor04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Orcinus orca (killer whale)
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
oor04650  Natural killer cell mediated cytotoxicity
oor04650

Other DBs
GO: 0042267
Organism
Orcinus orca (killer whale) [GN:oor]
Gene
101276044  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
101276292  KLRD1; natural killer cells antigen CD94 [KO:K06516]
101289268  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
101288182  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X5 [KO:K07293] [EC:3.1.3.48]
101276958  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
101288922  ICAM2; intercellular adhesion molecule 2 isoform X1 [KO:K06523]
101278885  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
101285903  ITGB2; integrin beta-2 isoform X3 [KO:K06464]
101281402  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
101290166  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
101269690  VAV2; guanine nucleotide exchange factor VAV2 isoform X11 [KO:K05730]
101282339  VAV1; LOW QUALITY PROTEIN: proto-oncogene vav [KO:K05730]
101274018  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X3 [KO:K04392]
101269741  RAC2; ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
101278177  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
101288086  PAK1; serine/threonine-protein kinase PAK 1 isoform X2 [KO:K04409] [EC:2.7.11.1]
101286388  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101287162  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
101273287  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
101289394  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101269870  TNF; tumor necrosis factor [KO:K03156]
101286998  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101282933  IFNG; interferon gamma [KO:K04687]
101286938  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
101271418  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
101270000  low affinity immunoglobulin gamma Fc region receptor III-A-like isoform X1 [KO:K06463]
125964005  low affinity immunoglobulin gamma Fc region receptor III-A-like isoform X1 [KO:K06463]
101270339  NCR1; natural cytotoxicity triggering receptor 1 [KO:K06741]
101269371  NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]
101277161  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101281326  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
101286910  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
101281971  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
101274029  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
101270618  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
101278886  LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356]
101281412  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
101285216  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101269683  SH3BP2; SH3 domain-binding protein 2 isoform X5 [KO:K07984]
101278075  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101278974  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
101283011  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101277568  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101285437  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101281352  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta isoform X2 [KO:K02649]
101279266  FYN; tyrosine-protein kinase Fyn isoform X2 [KO:K05703] [EC:2.7.10.2]
101276908  SHC1; SHC-transforming protein 1 isoform X2 [KO:K06279]
101275665  SHC2; SHC-transforming protein 2 isoform X1 [KO:K17447]
101280480  SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448]
101289594  SHC4; SHC-transforming protein 4 isoform X4 [KO:K17449]
101271441  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101286587  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
105748221  LOW QUALITY PROTEIN: son of sevenless homolog 2-like [KO:K03099]
101284580  SOS2; son of sevenless homolog 2 isoform X2 [KO:K03099]
101271947  GTPase HRas-like isoform X4 [KO:K02833]
101286301  HRAS; GTPase HRas isoform X2 [KO:K02833]
101281897  KRAS; GTPase KRas isoform X2 [KO:K07827]
101276138  NRAS; GTPase NRas [KO:K07828]
101271966  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
101277195  BRAF; serine/threonine-protein kinase B-raf isoform X4 [KO:K04365] [EC:2.7.11.1]
101272984  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
101275067  LOW QUALITY PROTEIN: MHC class I polypeptide-related sequence B [KO:K07985]
101287791  LOW QUALITY PROTEIN: MHC class I polypeptide-related sequence B-like [KO:K07985]
101290103  HCST; hematopoietic cell signal transducer [KO:K07988]
101283387  CD48; CD48 antigen [KO:K06479]
101274895  CD244; natural killer cell receptor 2B4 [KO:K06582]
101271019  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
101278517  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X3 [KO:K04348] [EC:3.1.3.16]
101286888  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
105748080  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
101272877  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101283533  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
101289855  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101276350  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
101277002  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101276418  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
101285633  SH2D1B; SH2 domain-containing protein 1B isoform X1 [KO:K07989]
101276716  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
101276054  IFNGR1; interferon gamma receptor 1 [KO:K05132]
101279441  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
101274041  interferon alpha-1-like [KO:K05414]
101275016  interferon alpha-1-like [KO:K05414]
101275275  interferon alpha-1-like [KO:K05414]
101287367  interferon alpha-3-like [KO:K05414]
125964698  interferon alpha-1-like [KO:K05414]
125964699  interferon alpha-1-like [KO:K05414]
125964701  interferon alpha-3-like [KO:K05414]
125964702  interferon alpha-3-like [KO:K05414]
125964703  interferon alpha-3-like [KO:K05414]
101289058  IFNB1; interferon beta [KO:K05415]
101284215  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101283958  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
101282902  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X2 [KO:K04721]
101271509  tumor necrosis factor receptor superfamily member 10A isoform X9 [KO:K04722]
101272436  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
101284022  FAS; tumor necrosis factor receptor superfamily member 6 isoform X5 [KO:K04390]
101287187  granzyme B isoform X1 [KO:K01353] [EC:3.4.21.79]
101289025  PRF1; perforin-1 [KO:K07818]
101289847  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
101277745  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
101281374  LOW QUALITY PROTEIN: 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
oor04010  MAPK signaling pathway
oor04020  Calcium signaling pathway
oor04060  Cytokine-cytokine receptor interaction
oor04210  Apoptosis
oor04630  JAK-STAT signaling pathway
KO pathway
ko04650   
LinkDB

DBGET integrated database retrieval system