KEGG   PATHWAY: prob04650
Entry
prob04650                   Pathway                                
Name
Natural killer cell mediated cytotoxicity - Phodopus roborovskii (desert hamster)
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
prob04650  Natural killer cell mediated cytotoxicity
prob04650

Other DBs
GO: 0042267
Organism
Phodopus roborovskii (desert hamster) [GN:prob]
Gene
127238507  killer cell immunoglobulin-like receptor 3DL1 [KO:K07980]
127238508  killer cell immunoglobulin-like receptor 3DL1 [KO:K07980]
127213012  NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
127213003  natural killer cells antigen CD94 [KO:K06516]
127213039  Ptpn6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
127216041  Ptpn11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
127231412  Icam1; intercellular adhesion molecule 1 [KO:K06490]
127218315  Icam2; intercellular adhesion molecule 2 [KO:K06523]
127228383  Itgal; LOW QUALITY PROTEIN: integrin alpha-L [KO:K05718]
127224137  Itgb2; integrin beta-2 [KO:K06464]
127230243  Ptk2b; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
127222667  Vav2; guanine nucleotide exchange factor VAV2 [KO:K05730]
127216807  Vav1; proto-oncogene vav [KO:K05730]
127216834  Vav3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
127237270  Rac1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
127225755  Rac2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
127220446  Rac3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
127227928  Pak1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
127231875  Map2k1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
127216563  Map2k2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
127228340  Mapk3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
127216731  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
127226948  Mapk1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
127224347  Tnf; tumor necrosis factor [KO:K03156]
127219779  Csf2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
127215720  Ifng; interferon gamma [KO:K04687]
127238750  Tyrobp; TYRO protein tyrosine kinase-binding protein [KO:K07992]
127225402  Lck; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
127223278  low affinity immunoglobulin gamma Fc region receptor III-A [KO:K06463]
127215594  LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 1-like [KO:K06741]
127238420  LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 1-like [KO:K06741]
127223873  Ncr3; natural cytotoxicity triggering receptor 3 [KO:K06743]
127223569  Fcer1g; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
127223521  Cd247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
127236756  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
127229235  Syk; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
127219433  Lcp2; lymphocyte cytosolic protein 2 [KO:K07361]
127228326  Lat; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
127236900  Lat2; linker for activation of T-cells family member 2 [KO:K26356]
127224331  Plcg1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
127234658  Plcg2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
127233803  Sh3bp2; SH3 domain-binding protein 2 [KO:K07984]
127223328  Pik3ca; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
127238024  Pik3cb; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
127213428  Pik3cd; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
127217216  Pik3r2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
127225197  Pik3r3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
127220972  Pik3r1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
127215149  Fyn; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
127233113  Shc1; SHC-transforming protein 1 isoform X1 [KO:K06279]
127216670  Shc2; SHC-transforming protein 2 [KO:K17447]
127229241  Shc3; SHC-transforming protein 3 [KO:K17448]
127221520  Shc4; SHC-transforming protein 4 [KO:K17449]
127219174  Grb2; growth factor receptor-bound protein 2 [KO:K04364]
127217013  Sos1; son of sevenless homolog 1 [KO:K03099]
127230645  Sos2; son of sevenless homolog 2 isoform X1 [KO:K03099]
127228530  Hras; GTPase HRas [KO:K02833]
127213087  Kras; GTPase KRas isoform X1 [KO:K07827]
127233129  Nras; GTPase NRas [KO:K07828]
127214235  Braf; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
127236205  Raf1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
127237658  UL16-binding protein 1-like [KO:K07986]
127237690  LOW QUALITY PROTEIN: UL16-binding protein 1-like [KO:K07986]
127212993  Klrk1; NKG2-D type II integral membrane protein [KO:K06728]
127238555  Hcst; hematopoietic cell signal transducer isoform X1 [KO:K07988]
127223594  Cd48; CD48 antigen [KO:K06479]
127223589  Cd244; natural killer cell receptor 2B4 isoform X1 [KO:K06582]
127222969  Ppp3ca; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
127230207  Ppp3cc; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127214138  Ppp3cb; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
127224691  Ppp3r2; calcineurin subunit B type 2 [KO:K06268]
127233971  Ppp3r1; calcineurin subunit B type 1 [KO:K06268]
127235061  Nfatc1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
127223216  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
127225333  nuclear factor of activated T-cells, cytoplasmic 2-like [KO:K17332]
127218483  Prkca; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
127228289  Prkcb; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
127238613  Prkcg; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
127223550  Sh2d1b; SH2 domain-containing protein 1B [KO:K07989]
127218102  Sh2d1a; SH2 domain-containing protein 1A isoform X1 [KO:K07990]
127215047  Ifngr1; interferon gamma receptor 1 [KO:K05132]
127227515  Ifngr2; interferon gamma receptor 2 [KO:K05133]
127224801  interferon alpha-9-like [KO:K05414]
127224803  interferon alpha-12-like [KO:K05414]
127224841  interferon alpha-12 [KO:K05414]
127224844  interferon alpha-12 [KO:K05414]
127224845  interferon alpha-13-like [KO:K05414]
127224846  interferon alpha-12-like [KO:K05414]
127224847  interferon alpha-12-like [KO:K05414]
127224848  interferon alpha-12-like [KO:K05414]
127224849  interferon alpha-12-like [KO:K05414]
127224840  Ifnb1; interferon beta [KO:K05415]
127227514  Ifnar1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
127227512  Ifnar2; interferon alpha/beta receptor 2 [KO:K05131]
127223363  Tnfsf10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
127230045  tumor necrosis factor receptor superfamily member 10B [KO:K04722]
127223236  Faslg; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
127233374  Fas; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
127230350  granzyme B [KO:K01353] [EC:3.4.21.79]
127223888  Prf1; perforin-1 [KO:K07818]
127220536  Casp3; caspase-3 [KO:K02187] [EC:3.4.22.56]
127236186  Bid; BH3-interacting domain death agonist [KO:K04726]
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
prob04010  MAPK signaling pathway
prob04020  Calcium signaling pathway
prob04060  Cytokine-cytokine receptor interaction
prob04210  Apoptosis
prob04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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