KEGG   PATHWAY: setr04650
Entry
setr04650                   Pathway                                
Name
Natural killer cell mediated cytotoxicity - Suncus etruscus (white-toothed pygmy shrew)
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
setr04650  Natural killer cell mediated cytotoxicity
setr04650

Other DBs
GO: 0042267
Organism
Suncus etruscus (white-toothed pygmy shrew) [GN:setr]
Gene
125996221  TNF; tumor necrosis factor [KO:K03156]
125996227  NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]
125997372  NRAS; GTPase NRas [KO:K07828]
125997407  VAV3; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV3 [KO:K05730]
125998044  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
125999018  SOS2; son of sevenless homolog 2 [KO:K03099]
125999103  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
125999333  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
126001136  ICAM2; intercellular adhesion molecule 2 [KO:K06523]
126001552  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
126001704  [KO:K01353] [EC:3.4.21.79]
126001706  [KO:K01353] [EC:3.4.21.79]
126001707  [KO:K01353] [EC:3.4.21.79]
126002199  [KO:K07293] [EC:3.1.3.48]
126002675  IFNB1; interferon beta [KO:K05415]
126003300  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform [KO:K04348] [EC:3.1.3.16]
126003375  SHC3; SHC-transforming protein 3 [KO:K17448]
126003376  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
126003551  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
126003615  [KO:K05414]
126003784  IFNA6; interferon alpha-6 [KO:K05414]
126004388  [KO:K04722]
126005876  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
126006104  PTK2B; LOW QUALITY PROTEIN: protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
126006381  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
126006542  PTPN6; tyrosine-protein phosphatase non-receptor type 6 [KO:K05697] [EC:3.1.3.48]
126006887  [KO:K02187] [EC:3.4.22.56]
126007206  [KO:K02187] [EC:3.4.22.56]
126007207  [KO:K02187] [EC:3.4.22.56]
126009330  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
126010754  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
126011086  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
126011131  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
126011432  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
126011501  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
126011898  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
126012035  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
126012036  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
126012641  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
126013242  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
126013731  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
126013862  CD48; CD48 antigen [KO:K06479]
126013988  [KO:K06463]
126014284  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
126014303  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
126014310  CD244; natural killer cell receptor 2B4 [KO:K06582]
126015875  [KO:K06856]
126017276  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
126017297  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
126017532  [KO:K04409] [EC:2.7.11.1]
126019084  HRAS; GTPase HRas [KO:K02833]
126019129  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 [KO:K17332]
126020007  SHC4; SHC-transforming protein 4 [KO:K17449]
126020311  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
126020709  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
126021920  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
126022051  [KO:K06541]
126022053  [KO:K06541]
126022055  KLRD1; natural killer cells antigen CD94 [KO:K06516]
126022183  IFNG; interferon gamma [KO:K04687]
126022683  BID; BH3-interacting domain death agonist [KO:K04726]
126022823  KRAS; GTPase KRas isoform X1 [KO:K07827]
126023864  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
126024149  [KO:K07360] [EC:2.7.10.2]
126024674  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
126025796  IFNAR2; interferon alpha/beta receptor 2 [KO:K05131]
126025916  ITGB2; integrin beta-2 [KO:K06464]
126026058  [KO:K05130]
126026073  IFNGR2; interferon gamma receptor 2 [KO:K05133]
126026082  [KO:K05130]
126027269  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
126027678  TYROBP; TYRO protein tyrosine kinase-binding protein [KO:K07992]
126027688  HCST; hematopoietic cell signal transducer [KO:K07988]
126027877  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
126027978  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
126028224  [KO:K04348] [EC:3.1.3.16]
126029540  LAT; linker for activation of T-cells family member 1 [KO:K07362]
126029670  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
126029883  ITGAL; integrin alpha-L [KO:K05718]
126029893  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
126030162  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
126030200  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
126030488  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
126030826  SHC2; SHC-transforming protein 2 [KO:K17447]
126030861  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
126030878  PRF1; perforin-1 [KO:K07818]
126030882  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
126031062  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
126031136  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
126031410  IFNGR1; interferon gamma receptor 1 [KO:K05132]
126032044  SH3BP2; SH3 domain-binding protein 2 [KO:K07984]
126033704  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
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
setr04010  MAPK signaling pathway
setr04020  Calcium signaling pathway
setr04060  Cytokine-cytokine receptor interaction
setr04210  Apoptosis
setr04630  JAK-STAT signaling pathway
KO pathway
ko04650   

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