KEGG   PATHWAY: rro04650
Entry
rro04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Rhinopithecus roxellana (golden snub-nosed 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
rro04650  Natural killer cell mediated cytotoxicity
rro04650

Other DBs
GO: 0042267
Organism
Rhinopithecus roxellana (golden snub-nosed monkey) [GN:rro]
Gene
104674750  LOW QUALITY PROTEIN: killer cell immunoglobulin-like receptor 3DL1 [KO:K07980]
104681114  LOW QUALITY PROTEIN: killer cell immunoglobulin-like receptor 3DL1 [KO:K07980]
104675314  LOW QUALITY PROTEIN: killer cell immunoglobulin-like receptor 3DL3 [KO:K07980]
104672221  killer cell immunoglobulin-like receptor 3DS1 isoform X1 [KO:K07980]
104675306  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
104675316  putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 isoform X3 [KO:K07980]
104668626  KLRC1; LOW QUALITY PROTEIN: NKG2-A/NKG2-B type II integral membrane protein [KO:K06541]
104668620  KLRD1; natural killer cells antigen CD94 isoform X1 [KO:K06516]
104680085  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X2 [KO:K05697] [EC:3.1.3.48]
104674419  PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X2 [KO:K07293] [EC:3.1.3.48]
104670485  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
104675450  ICAM2; intercellular adhesion molecule 2 isoform X1 [KO:K06523]
104681602  ITGAL; LOW QUALITY PROTEIN: integrin alpha-L [KO:K05718]
104659958  ITGB2; integrin beta-2 [KO:K06464]
104673947  PTK2B; protein-tyrosine kinase 2-beta isoform X1 [KO:K05871] [EC:2.7.10.2]
104669784  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
104665356  VAV1; proto-oncogene vav [KO:K05730]
104671354  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
104665823  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
104682502  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
104654979  RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
104664316  PAK1; serine/threonine-protein kinase PAK 1 isoform X5 [KO:K04409] [EC:2.7.11.1]
104662575  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
104665487  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
104676897  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
104681150  MAPK3; LOW QUALITY PROTEIN: mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
104661913  TNF; tumor necrosis factor isoform X1 [KO:K03156]
104659848  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
104664085  IFNG; interferon gamma [KO:K04687]
104668623  NKG2-C type II integral membrane protein isoform X2 [KO:K24233]
104668625  NKG2-C type II integral membrane protein isoform X2 [KO:K24233]
104679038  NCR2; LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 2 [KO:K06742]
104666669  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X2 [KO:K07992]
104654761  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
104664696  LOW QUALITY PROTEIN: uncharacterized protein LOC104664696 [KO:K06856]
104674294  LOW QUALITY PROTEIN: uncharacterized protein LOC104674294 [KO:K06856]
104677074  uncharacterized protein LOC104677074 [KO:K06856]
104671953  LOW QUALITY PROTEIN: low affinity immunoglobulin gamma Fc region receptor III [KO:K06463]
104674749  NCR1; natural cytotoxicity triggering receptor 1 isoform X1 [KO:K06741]
104661915  NCR3; natural cytotoxicity triggering receptor 3 isoform X3 [KO:K06743]
104665342  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
104668979  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X3 [KO:K06453]
104661474  tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
104662008  SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
104663606  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
104682138  LAT; linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
104681245  LAT2; linker for activation of T-cells family member 2 [KO:K26356]
104672220  PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
104671624  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
104678949  SH3BP2; SH3 domain-binding protein 2 isoform X2 [KO:K07984]
104663050  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104665061  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
104670605  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
104662124  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
104675620  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
104680672  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
104668854  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
104663483  SHC1; SHC-transforming protein 1 isoform X1 [KO:K06279]
104668515  SHC3; SHC-transforming protein 3 isoform X1 [KO:K17448]
104657941  SHC4; SHC-transforming protein 4 [KO:K17449]
104681311  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
104663024  SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]
104682751  SOS2; son of sevenless homolog 2 isoform X1 [KO:K03099]
104654600  HRAS; GTPase HRas isoform X1 [KO:K02833]
104670041  KRAS; GTPase KRas isoform X1 [KO:K07827]
104669078  NRAS; GTPase NRas [KO:K07828]
104664593  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
104659700  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
104673299  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
104661906  MHC class I polypeptide-related sequence B [KO:K07985]
104656725  MHC class I polypeptide-related sequence B-like [KO:K07985]
104663743  UL16-binding protein 1 [KO:K07986]
104678340  UL16-binding protein 2 [KO:K07986]
104678341  UL16-binding protein 3-like [KO:K07986]
104678343  ULBP3; UL16-binding protein 3 [KO:K07986]
104676273  UL16-binding protein 2-like [KO:K07986]
104678356  LOW QUALITY PROTEIN: UL16-binding protein 1 [KO:K07986]
115897035  UL16-binding protein 1-like [KO:K07986]
115897046  UL16-binding protein 1-like [KO:K07986]
104663744  UL16-binding protein 1-like [KO:K07986]
104668621  NKG2-D type II integral membrane protein [KO:K06728]
104666667  HCST; hematopoietic cell signal transducer isoform X1 [KO:K07988]
104660389  CD48; CD48 antigen isoform X1 [KO:K06479]
104674092  CD244; natural killer cell receptor 2B4 isoform X2 [KO:K06582]
104663969  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
104663623  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
104669965  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
104675975  PPP3R1; calcineurin subunit B type 1 isoform X1 [KO:K06268]
104670806  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
104653917  calcineurin subunit B type 1 [KO:K06268]
104667797  NFATC1; LOW QUALITY PROTEIN: nuclear factor of activated T-cells, cytoplasmic 1 [KO:K04446]
104662367  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
104675428  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
104665907  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
104676027  PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
104663734  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
104679567  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
104675021  IFNGR1; interferon gamma receptor 1 [KO:K05132]
104658778  IFNGR2; interferon gamma receptor 2 isoform X1 [KO:K05133]
104670273  interferon alpha-1/13 [KO:K05414]
104670275  IFNA8; interferon alpha-8 [KO:K05414]
104670276  interferon alpha-1/13-like [KO:K05414]
104670278  IFNA6; interferon alpha-6 [KO:K05414]
104670280  interferon alpha-14 [KO:K05414]
104670290  interferon alpha-4 [KO:K05414]
104670292  interferon alpha-10-like [KO:K05414]
104680728  interferon alpha-10 [KO:K05414]
115893964  interferon alpha-4 [KO:K05414]
115893973  interferon alpha-10-like [KO:K05414]
104670295  IFNB1; interferon beta [KO:K05415]
104658750  IFNAR1; interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
104658748  IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
104657165  TNFSF10; tumor necrosis factor ligand superfamily member 10 isoform X1 [KO:K04721]
104663984  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A [KO:K04722]
104663979  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B isoform X1 [KO:K04722]
104669600  FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]
104675147  FAS; tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
104662660  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
104661986  PRF1; perforin-1 [KO:K07818]
104666783  caspase-3-like [KO:K02187] [EC:3.4.22.56]
104673791  CASP3; caspase-3 [KO:K02187] [EC:3.4.22.56]
104676299  BID; BH3-interacting domain death agonist isoform X1 [KO:K04726]
104676268  RAET1E; retinoic acid early transcript 1E [KO:K07987]
104676269  RAET1G; UL-16 binding protein 5 [KO:K07987]
104676270  uncharacterized protein LOC104676270 isoform X1 [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
rro04010  MAPK signaling pathway
rro04020  Calcium signaling pathway
rro04060  Cytokine-cytokine receptor interaction
rro04210  Apoptosis
rro04630  JAK-STAT signaling pathway
KO pathway
ko04650   
LinkDB

DBGET integrated database retrieval system