KEGG   PATHWAY: mcc04650
Entry
mcc04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Macaca mulatta (rhesus monkey)
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
mcc04650  Natural killer cell mediated cytotoxicity
mcc04650

Other DBs
GO: 0042267
Organism
Macaca mulatta (rhesus monkey) [GN:mcc]
Gene
100141395  CD9; CD9 antigen [KO:K07985]
100423877  IFNGR1; interferon gamma receptor 1 precursor [KO:K05132]
100424246  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
100426724  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
100428682  PPP3R1; calcineurin subunit B type 1 isoform X3 [KO:K06268]
106992322  [KO:K05414]
106995851  IFNA6; interferon alpha-6 [KO:K05414]
106996003  [KO:K06856]
106998081  [KO:K07987]
106999628  [KO:K06856]
114670780  KLRC2; NKG2-C type II integral membrane protein [KO:K24233]
114672663  [KO:K05414]
114672664  [KO:K05414]
114675805  [KO:K06856]
114679736  [KO:K06856]
574145  KLRD1; natural killer cells antigen CD94 [KO:K06516]
574146  KLRC1; NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
574152  HCST; hematopoietic cell signal transducer precursor [KO:K07988]
574156  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
574158  ICAM2; intercellular adhesion molecule 2 precursor [KO:K06523]
574159  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
574207  TYROBP; TYRO protein tyrosine kinase-binding protein precursor [KO:K07992]
574214  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
574240  NKG2D; NKG2-D type II integral membrane protein [KO:K06728]
574242  NCR1; natural cytotoxicity triggering receptor 1 precursor [KO:K06741]
574258  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
574275  SHC3; SHC-transforming protein 3 [KO:K17448]
574282  IFNG; interferon gamma precursor [KO:K04687]
574332  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
574371  CSF2; granulocyte-macrophage colony-stimulating factor precursor [KO:K05427]
693554  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
693676  LAT2; linker for activation of T-cells family member 2 precursor [KO:K26356]
693869  NCR2; natural cytotoxicity triggering receptor 2 [KO:K06742]
694076  [KO:K07987]
694135  [KO:K07986]
694216  [KO:K07986]
694341  [KO:K07986]
694451  TNFSF10; tumor necrosis factor ligand superfamily member 10 precursor [KO:K04721]
694466  [KO:K07986]
694473  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
694525  [KO:K07986]
694600  [KO:K07986]
694631  [KO:K05414]
694685  VAV3; guanine nucleotide exchange factor VAV3 isoform X2 [KO:K05730]
694725  RAF1; RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
695031  [KO:K07987]
696709  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
697069  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
697814  CD247; T-cell surface glycoprotein CD3 zeta chain precursor [KO:K06453]
698089  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
698569  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
698585  PAK1; serine/threonine-protein kinase PAK 1 isoform X5 [KO:K04409] [EC:2.7.11.1]
698830  HRAS; GTPase HRas [KO:K02833]
698996  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
699489  IFNGR2; interferon gamma receptor 2 [KO:K05133]
699604  IFNAR1; interferon alpha/beta receptor 1 precursor [KO:K05130]
699726  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
700374  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
700932  SH3BP2; SH3 domain-binding protein 2 isoform X3 [KO:K07984]
701195  PRKCB; protein kinase C beta type [KO:K19662] [EC:2.7.11.13]
702041  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
704102  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
704656  LAT; linker for activation of T-cells family member 1 isoform X2 [KO:K07362]
705601  SOS2; son of sevenless homolog 2 [KO:K03099]
706955  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X7 [KO:K04348] [EC:3.1.3.16]
707169  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
707310  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
707555  [KO:K07360] [EC:2.7.10.2]
707977  KRAS; GTPase KRas [KO:K07827]
708233  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X2 [KO:K04348] [EC:3.1.3.16]
708938  MAPK3; mitogen-activated protein kinase 3 isoform X1 [KO:K04371] [EC:2.7.11.24]
709089  NRAS; GTPase NRas [KO:K07828]
709559  IFNA13; interferon alpha-1/13 precursor [KO:K05414]
709755  IFNA8; interferon alpha-8 [KO:K05414]
709773  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform [KO:K04348] [EC:3.1.3.16]
709948  IFNA2; interferon alpha-2 precursor [KO:K05414]
709959  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
710241  PRF1; perforin-1 [KO:K07818]
710415  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
710487  [KO:K05414]
710528  [KO:K05414]
710552  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
710568  [KO:K05414]
710577  ITGB2; integrin beta-2 isoform X1 [KO:K06464]
710601  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
710654  IFNA10; interferon alpha-4 precursor [KO:K05414]
710751  [KO:K05414]
710848  [KO:K05414]
711088  [KO:K05414]
711252  IFNA21; interferon alpha-21 [KO:K05414]
711414  IFNB1; interferon beta precursor [KO:K05415]
711945  ITGAL; integrin alpha-L isoform X2 [KO:K05718]
712044  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
712280  ICAM1; intercellular adhesion molecule 1 precursor [KO:K06490]
712787  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
713227  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
713777  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
714173  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
714374  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
714419  [KO:K06856]
714611  SHC4; SHC-transforming protein 4 [KO:K17449]
715141  MICB; MHC class I polypeptide-related sequence B precursor [KO:K07985]
715467  TNF; tumor necrosis factor [KO:K03156]
715574  NCR3; natural cytotoxicity triggering receptor 3 precursor [KO:K06743]
716098  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
716518  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
716650  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B isoform X1 [KO:K04722]
716826  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
717704  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
717755  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
718412  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
718982  SHC1; SHC-transforming protein 1 [KO:K06279]
719305  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
719367  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
719762  CD48; CD48 antigen isoform X1 [KO:K06479]
719800  CD244; natural killer cell receptor 2B4 isoform X2 [KO:K06582]
720006  FCGR3; low affinity immunoglobulin gamma Fc region receptor III isoform C precursor [KO:K06463]
720097  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
720263  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
720291  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma precursor [KO:K07983]
720452  [KO:K06856]
720904  [KO:K06856]
720935  [KO:K06856]
720985  [KO:K06856]
721002  [KO:K06856]
721021  SHC2; SHC-transforming protein 2 [KO:K17447]
721083  [KO:K06856]
721374  [KO:K07987]
721821  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 isoform X1 [KO:K04369] [EC:2.7.12.2]
722278  [KO:K06856]
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
mcc04010  MAPK signaling pathway
mcc04020  Calcium signaling pathway
mcc04060  Cytokine-cytokine receptor interaction
mcc04210  Apoptosis
mcc04630  JAK-STAT signaling pathway
KO pathway
ko04650   

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