KEGG   PATHWAY: cjc04650
Entry
cjc04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Callithrix jacchus (white-tufted-ear marmoset)
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
cjc04650  Natural killer cell mediated cytotoxicity
cjc04650

Other DBs
GO: 0042267
Organism
Callithrix jacchus (white-tufted-ear marmoset) [GN:cjc]
Gene
100385803  NCR1; natural cytotoxicity triggering receptor 1 [KO:K06741]
100386369  PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
100386452  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X5 [KO:K04348] [EC:3.1.3.16]
100386516  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
100387059  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
100387372  [KO:K05414]
100387394  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
100387570  CASP3; caspase-3 isoform X2 [KO:K02187] [EC:3.4.22.56]
100387926  [KO:K06463]
100387961  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
100388148  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
100388391  IFNB1; interferon beta [KO:K05415]
100388432  VAV1; proto-oncogene vav [KO:K05730]
100388952  IFNG; interferon gamma precursor [KO:K04687]
100389206  GZMB; granzyme B precursor [KO:K01353] [EC:3.4.21.79]
100389763  IFNGR2; interferon gamma receptor 2 [KO:K05133]
100390165  VAV3; guanine nucleotide exchange factor VAV3 isoform X4 [KO:K05730]
100390201  [KO:K05414]
100390337  SHC1; SHC-transforming protein 1 isoform X5 [KO:K06279]
100390347  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
100390790  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
100390841  [KO:K07985]
100390922  [KO:K07360] [EC:2.7.10.2]
100391434  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
100391655  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X2 [KO:K00922] [EC:2.7.1.153]
100391814  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100391922  NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]
100392220  SHC4; SHC-transforming protein 4 [KO:K17449]
100392639  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
100392970  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
100392986  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
100393276  HCST; hematopoietic cell signal transducer isoform X3 [KO:K07988]
100393633  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
100393866  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
100393991  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
100394035  [KO:K07985]
100394477  [KO:K07986]
100394657  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
100394834  [KO:K07986]
100395636  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
100395682  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
100395977  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A isoform X1 [KO:K04722]
100396000  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
100396491  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
100397065  [KO:K04722]
100397206  LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356]
100397442  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B isoform X2 [KO:K04722]
100397484  TNF; tumor necrosis factor [KO:K03156]
100397497  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
100397660  KLRC1; NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
100397803  FAS; tumor necrosis factor receptor superfamily member 6 precursor [KO:K04390]
100398258  KLRC2; NKG2-C type II integral membrane protein [KO:K24233]
100398849  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
100398970  KLRK1; NKG2-D type II integral membrane protein isoform 2 [KO:K06728]
100399584  KLRD1; natural killer cells antigen CD94 [KO:K06516]
100400700  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
100400756  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
100401717  SH3BP2; SH3 domain-binding protein 2 isoform X2 [KO:K07984]
100402406  SHC3; SHC-transforming protein 3 isoform X2 [KO:K17448]
100402685  ITGB2; integrin beta-2 isoform X2 [KO:K06464]
100403091  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
100403494  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
100403496  BID; BH3-interacting domain death agonist isoform X2 [KO:K04726]
100404028  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
100404109  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
100404210  PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]
100404764  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
100404815  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
100404817  PRF1; perforin-1 precursor [KO:K07818]
100404850  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
100405187  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X2 [KO:K04446]
100405329  CD48; CD48 antigen isoform X3 [KO:K06479]
100406017  HRAS; GTPase HRas [KO:K02833]
100406098  [KO:K05414]
100406408  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
100406428  CD244; natural killer cell receptor 2B4 isoform X2 [KO:K06582]
100406466  [KO:K05414]
100406689  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
100408363  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
100410124  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
100410136  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
100410164  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
100410231  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
100410306  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
100410584  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
100411766  RAET1E; retinoic acid early transcript 1E isoform X2 [KO:K07987]
100412464  [KO:K07986]
100414442  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
100414504  ICAM2; intercellular adhesion molecule 2 [KO:K06523]
100414516  [KO:K05414]
100414659  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X2 [KO:K02649]
100414782  NRAS; GTPase NRas isoform X2 [KO:K07828]
100414856  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
100414905  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X3 [KO:K07293] [EC:3.1.3.48]
100414931  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
100415083  SHC2; SHC-transforming protein 2 [KO:K17447]
100415300  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
100415678  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
100895294  [KO:K04392]
100896810  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
103793369  [KO:K05414]
103793556  [KO:K06856]
108587728  [KO:K07986]
108591807  [KO:K07828]
118144179  KRAS; GTPase KRas isoform X2 [KO:K07827]
118153020  [KO:K07986]
118153021  [KO:K07986]
128928022  [KO:K07986]
128928024  IFNAR2; interferon alpha/beta receptor 2 isoform X2 [KO:K05131]
128928158  [KO:K05414]
128930768  [KO:K07986]
128931761  NCR2; LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 2 [KO:K06742]
128931844  [KO:K07986]
128932203  [KO:K05414]
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
cjc04010  MAPK signaling pathway
cjc04020  Calcium signaling pathway
cjc04060  Cytokine-cytokine receptor interaction
cjc04210  Apoptosis
cjc04630  JAK-STAT signaling pathway
KO pathway
ko04650   

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