KEGG   PATHWAY: biu04650
Entry
biu04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Bos indicus (zebu cattle)
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
biu04650  Natural killer cell mediated cytotoxicity
biu04650

Other DBs
GO: 0042267
Organism
Bos indicus (zebu cattle) [GN:biu]
Gene
109571857  LOW QUALITY PROTEIN: putative killer cell immunoglobulin-like receptor like protein KIR3DP1 [KO:K07980]
109559659  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
109559660  LOW QUALITY PROTEIN: NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
109559662  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
109558578  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
109558579  uncharacterized protein LOC109558579 [KO:K06541]
109559666  natural killer cells antigen CD94 isoform X1 [KO:K06516]
109559668  natural killer cells antigen CD94-like isoform X1 [KO:K06516]
109558908  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
109570927  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
109570168  tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
109561581  intercellular adhesion molecule 1 [KO:K06490]
109573936  ICAM2; intercellular adhesion molecule 2 isoform X1 [KO:K06523]
109573938  intercellular adhesion molecule 2-like isoform X1 [KO:K06523]
109578145  ITGAL; integrin alpha-L [KO:K05718]
109560786  ITGB2; integrin beta-2 [KO:K06464]
109563157  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
109565687  VAV2; LOW QUALITY PROTEIN: guanine nucleotide exchange factor VAV2 [KO:K05730]
109560955  VAV1; proto-oncogene vav [KO:K05730]
109556793  VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]
109578192  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
109559531  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
109574290  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
109554525  PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
109564697  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 isoform X1 [KO:K04368] [EC:2.7.12.2]
109561751  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
109578667  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
109570973  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
109577428  TNF; tumor necrosis factor [KO:K03156]
109561218  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
109558719  IFNG; interferon gamma [KO:K04687]
109572395  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
109572368  LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]
109578151  low affinity immunoglobulin gamma Fc region receptor III isoform X1 [KO:K06463]
109576829  NCR3; natural cytotoxicity triggering receptor 3 isoform X1 [KO:K06743]
109578311  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
109577671  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
109565800  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
109563281  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
109574975  LCP2; lymphocyte cytosolic protein 2 isoform X1 [KO:K07361]
109578681  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
109567698  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
109572707  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
109560737  SH3BP2; LOW QUALITY PROTEIN: SH3 domain-binding protein 2 [KO:K07984]
109559805  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]
109570415  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform [KO:K00922] [EC:2.7.1.153]
109557823  PIK3CA; LOW QUALITY PROTEIN: phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
109574805  PIK3R1; LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit alpha [KO:K02649]
109561418  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
109556345  phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
109563811  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
109553931  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
109561056  SHC2; SHC-transforming protein 2 [KO:K17447]
109562580  SHC3; SHC-transforming protein 3 [KO:K17448]
109565147  SHC4; SHC-transforming protein 4 [KO:K17449]
109574040  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
109566002  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
109564346  SOS2; son of sevenless homolog 2 [KO:K03099]
109560940  GTPase HRas-like [KO:K02833]
109559581  KRAS; GTPase KRas isoform X1 [KO:K07827]
109555890  NRAS; GTPase NRas [KO:K07828]
109555027  ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
109557698  BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
109576053  RAF1; LOW QUALITY PROTEIN: RAF proto-oncogene serine/threonine-protein kinase [KO:K04366] [EC:2.7.11.1]
109577075  MHC class I polypeptide-related sequence B-like isoform X1 [KO:K07985]
109577084  MHC class I polypeptide-related sequence B-like isoform X1 [KO:K07985]
109577087  MHC class I polypeptide-related sequence B-like isoform X1 [KO:K07985]
109563578  NKG2D ligand 3-like [KO:K07986]
109564019  NKG2D ligand 3-like [KO:K07986]
109564020  NKG2D ligand 3-like [KO:K07986]
109564038  NKG2D ligand 1-like [KO:K07986]
109564044  NKG2D ligand 1-like isoform X1 [KO:K07986]
109564043  NKG2D ligand 3-like [KO:K07986]
109559665  NKG2-D type II integral membrane protein [KO:K06728]
109572413  HCST; hematopoietic cell signal transducer [KO:K07988]
109578523  CD48; CD48 antigen [KO:K06479]
109578461  CD244; natural killer cell receptor 2B4 isoform X1 [KO:K06582]
109563107  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109553732  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109560300  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
109566227  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
109563306  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
109577750  NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
109567554  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
109573366  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
109578560  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
109572998  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
109577968  SH2D1B; SH2 domain-containing protein 1B isoform X1 [KO:K07989]
109563984  IFNGR1; interferon gamma receptor 1 [KO:K05132]
109569763  IFNGR2; interferon gamma receptor 2 [KO:K05133]
109562847  interferon alpha-H [KO:K05414]
109562638  interferon alpha-G-like [KO:K05414]
109562641  LOW QUALITY PROTEIN: interferon alpha-1-like [KO:K05414]
109562644  interferon alpha-F [KO:K05414]
109562652  interferon alpha-A [KO:K05414]
109562656  interferon alpha-H-like [KO:K05414]
109562659  interferon alpha-H-like [KO:K05414]
109562660  interferon alpha-H-like [KO:K05414]
109562665  interferon alpha-B-like [KO:K05414]
109562668  interferon alpha-2-like [KO:K05414]
109562670  interferon alpha-2-like [KO:K05414]
109562673  interferon alpha-3-like [KO:K05414]
109562852  interferon beta-2-like [KO:K05415]
109562853  interferon beta-1-like [KO:K05415]
109562855  interferon beta-1 [KO:K05415]
109562667  LOW QUALITY PROTEIN: interferon beta-3-like [KO:K05415]
109562671  interferon beta-2-like [KO:K05415]
109562674  interferon beta-2 [KO:K05415]
109562675  interferon beta-2-like [KO:K05415]
109570535  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
109572614  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
109558018  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
109563119  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
109570480  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
109570785  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
109579171  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
109575715  duodenase-1 isoform X1 [KO:K01353] [EC:3.4.21.79]
109575716  mast cell protease 1A-like [KO:K01353] [EC:3.4.21.79]
109575719  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
109575720  duodenase-1-like [KO:K01353] [EC:3.4.21.79]
109575204  LOW QUALITY PROTEIN: mast cell protease 3-like [KO:K01353] [EC:3.4.21.79]
109575773  duodenase-1 [KO:K01353] [EC:3.4.21.79]
109575279  granzyme B-like [KO:K01353] [EC:3.4.21.79]
109553933  PRF1; perforin-1 [KO:K07818]
109553316  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
109559782  BH3-interacting domain death agonist-like isoform X1 [KO:K04726]
109559783  BH3-interacting domain death agonist-like isoform X1 [KO:K04726]
109564041  NKG2D ligand 4-like [KO:K07987]
109564047  NKG2D ligand 4-like [KO:K07987]
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
biu04010  MAPK signaling pathway
biu04020  Calcium signaling pathway
biu04060  Cytokine-cytokine receptor interaction
biu04210  Apoptosis
biu04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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