KEGG   PATHWAY: lve04650
Entry
lve04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Lipotes vexillifer (Yangtze River dolphin)
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
lve04650  Natural killer cell mediated cytotoxicity
lve04650

Other DBs
GO: 0042267
Organism
Lipotes vexillifer (Yangtze River dolphin) [GN:lve]
Gene
103074952  KLRC1; NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
103091175  KLRD1; natural killer cells antigen CD94 [KO:K06516]
103086882  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
103088783  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
103079699  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
103078665  ICAM2; intercellular adhesion molecule 2 [KO:K06523]
103086254  ITGAL; integrin alpha-L isoform X1 [KO:K05718]
103079755  ITGB2; integrin beta-2 [KO:K06464]
103083166  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
103082841  VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]
103084985  VAV1; proto-oncogene vav isoform X1 [KO:K05730]
103088874  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
103074749  RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]
103076541  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
103079514  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
103072869  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
103082805  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
103090769  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
103070260  MAPK1; mitogen-activated protein kinase 1 isoform X1 [KO:K04371] [EC:2.7.11.24]
103075543  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
103083231  TNF; tumor necrosis factor [KO:K03156]
103089107  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
103085542  IFNG; interferon gamma [KO:K04687]
103077346  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
103069516  LCK; tyrosine-protein kinase Lck isoform X1 [KO:K05856] [EC:2.7.10.2]
103075075  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8-like [KO:K06856]
103075361  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8-like [KO:K06856]
103068717  low affinity immunoglobulin gamma Fc region receptor III-like [KO:K06463]
103086505  NCR1; natural cytotoxicity triggering receptor 1 [KO:K06741]
103082419  NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]
103085198  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
103076558  CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]
103074297  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
103079796  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
103079539  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
103084123  LAT; linker for activation of T-cells family member 1 [KO:K07362]
103075887  LAT2; linker for activation of T-cells family member 2 [KO:K26356]
103068930  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
103070997  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
103070617  SH3BP2; SH3 domain-binding protein 2 isoform X1 [KO:K07984]
103089257  PIK3CD; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
103088756  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
103085303  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
103070370  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
103078725  PIK3R3; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
103083960  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
103071829  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
103074885  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
103088833  SHC2; SHC-transforming protein 2 [KO:K17447]
103078122  SHC3; SHC-transforming protein 3 [KO:K17448]
103088900  SHC4; SHC-transforming protein 4 isoform X1 [KO:K17449]
103079766  GRB2; growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
103079242  SOS1; son of sevenless homolog 1 [KO:K03099]
103081084  SOS2; son of sevenless homolog 2-like [KO:K03099]
103076043  HRAS; GTPase HRas isoform X1 [KO:K02833]
103077579  KRAS; GTPase KRas [KO:K07827]
103068734  NRAS; GTPase NRas [KO:K07828]
103090018  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
103079256  BRAF; serine/threonine-protein kinase B-raf [KO:K04365] [EC:2.7.11.1]
103087933  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
103077069  HCST; hematopoietic cell signal transducer [KO:K07988]
103077770  CD48; CD48 antigen [KO:K06479]
103088417  CD244; natural killer cell receptor 2B4 [KO:K06582]
103088182  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103070526  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103090427  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
103078845  PPP3R2; LOW QUALITY PROTEIN: calcineurin subunit B type 2 [KO:K06268]
103068473  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
103081110  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
103083433  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
103073028  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
103090549  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
103086653  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
103085710  SH2D1B; LOW QUALITY PROTEIN: SH2 domain-containing protein 1B [KO:K07989]
103084312  SH2D1A; SH2 domain-containing protein 1A isoform X1 [KO:K07990]
103082113  IFNGR1; LOW QUALITY PROTEIN: interferon gamma receptor 1 [KO:K05132]
103081741  IFNGR2; LOW QUALITY PROTEIN: interferon gamma receptor 2 [KO:K05133]
103073219  LOW QUALITY PROTEIN: interferon alpha-8-like [KO:K05414]
103090661  interferon alpha-1-like [KO:K05414]
103091202  interferon alpha-1-like [KO:K05414]
103068617  interferon alpha-1-like [KO:K05414]
103069181  interferon alpha-1-like [KO:K05414]
103069739  interferon alpha-1-like [KO:K05414]
103073772  interferon beta-2-like [KO:K05415]
103068842  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
103069127  IFNAR2; LOW QUALITY PROTEIN: interferon alpha/beta receptor 2 [KO:K05131]
103083521  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
103089274  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
103076248  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
103075576  tumor necrosis factor receptor superfamily member 10A-like [KO:K04722]
103073066  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
103080104  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
103087729  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
103088275  LOW QUALITY PROTEIN: mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
103076813  PRF1; perforin-1 [KO:K07818]
103073819  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
103078531  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
lve04010  MAPK signaling pathway
lve04020  Calcium signaling pathway
lve04060  Cytokine-cytokine receptor interaction
lve04210  Apoptosis
lve04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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