KEGG   PATHWAY: sbq04650
Entry
sbq04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Saimiri boliviensis boliviensis (Bolivian squirrel 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
sbq04650  Natural killer cell mediated cytotoxicity
sbq04650

Other DBs
GO: 0042267
Organism
Saimiri boliviensis boliviensis (Bolivian squirrel monkey) [GN:sbq]
Gene
101053728  killer cell immunoglobulin-like receptor 3DL3 isoform X1 [KO:K07980]
101036624  killer cell immunoglobulin-like receptor 3DL2 isoform X1 [KO:K07980]
101035987  killer cell immunoglobulin-like receptor 3DL2 [KO:K07980]
101046418  killer cell immunoglobulin-like receptor 3DL1 [KO:K07980]
104650262  LOW QUALITY PROTEIN: putative killer cell immunoglobulin-like receptor-like protein KIR3DX1 [KO:K07980]
101046441  KLRC1; NKG2-A/NKG2-B type II integral membrane protein isoform X1 [KO:K06541]
101045904  KLRD1; natural killer cells antigen CD94 [KO:K06516]
101032306  PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X4 [KO:K05697] [EC:3.1.3.48]
101031381  PTPN11; tyrosine-protein phosphatase non-receptor type 11 [KO:K07293] [EC:3.1.3.48]
101033019  LOW QUALITY PROTEIN: tyrosine-protein phosphatase non-receptor type 11-like [KO:K07293] [EC:3.1.3.48]
101054438  ICAM1; intercellular adhesion molecule 1 [KO:K06490]
101042874  ICAM2; intercellular adhesion molecule 2 isoform X1 [KO:K06523]
101049788  ITGAL; integrin alpha-L [KO:K05718]
101053620  ITGB2; integrin beta-2 [KO:K06464]
101032561  PTK2B; protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
101054437  VAV1; proto-oncogene vav [KO:K05730]
101037400  guanine nucleotide exchange factor VAV3 [KO:K05730]
101038097  VAV2; guanine nucleotide exchange factor VAV2 [KO:K05730]
104652250  VAV3; guanine nucleotide exchange factor VAV3 isoform X1 [KO:K05730]
101042808  RAC1; ras-related C3 botulinum toxin substrate 1 [KO:K04392]
101029481  RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]
101046124  RAC3; ras-related C3 botulinum toxin substrate 3 [KO:K07861]
101042666  PAK1; serine/threonine-protein kinase PAK 1 isoform X1 [KO:K04409] [EC:2.7.11.1]
101040361  MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]
101036151  MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
101038546  MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]
101043202  MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
101031357  TNF; tumor necrosis factor isoform X2 [KO:K03156]
101043583  CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]
101033464  IFNG; interferon gamma [KO:K04687]
101047280  NKG2-C type II integral membrane protein isoform X2 [KO:K24233]
101044135  NCR2; natural cytotoxicity triggering receptor 2 isoform X1 [KO:K06742]
101053468  TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
101041579  LCK; tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
101040997  LOW QUALITY PROTEIN: putative V-set and immunoglobulin domain-containing protein 7 [KO:K06856]
101054381  putative V-set and immunoglobulin domain-containing-like protein IGHV1OR21-1 [KO:K06856]
101033685  uncharacterized protein LOC101033685 [KO:K06856]
101041646  putative V-set and immunoglobulin domain-containing-like protein IGHV4OR15-8 [KO:K06856]
101040447  low affinity immunoglobulin gamma Fc region receptor III isoform X2 [KO:K06463]
101052345  NCR1; natural cytotoxicity triggering receptor 1 [KO:K06741]
101030417  NCR3; natural cytotoxicity triggering receptor 3 isoform X2 [KO:K06743]
101050914  FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
101046414  CD247; T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
101036932  ZAP70; tyrosine-protein kinase ZAP-70 [KO:K07360] [EC:2.7.10.2]
101031617  SYK; tyrosine-protein kinase SYK [KO:K05855] [EC:2.7.10.2]
101050038  LCP2; lymphocyte cytosolic protein 2 [KO:K07361]
101048116  LAT; linker for activation of T-cells family member 1 isoform X6 [KO:K07362]
101028207  LAT2; linker for activation of T-cells family member 2 isoform X4 [KO:K26356]
101046976  PLCG1; LOW QUALITY PROTEIN: 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]
101030999  PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]
101048243  SH3BP2; SH3 domain-binding protein 2 isoform X1 [KO:K07984]
101029768  PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
101052779  PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101027982  PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
101032496  PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]
101033359  PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
101050592  PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]
101051746  FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
101038895  SHC1; SHC-transforming protein 1 [KO:K06279]
101047748  SHC-transforming protein 1 [KO:K06279]
101048523  SHC2; SHC-transforming protein 2 [KO:K17447]
101028764  SHC3; SHC-transforming protein 3 [KO:K17448]
101032627  SHC4; SHC-transforming protein 4 [KO:K17449]
101038666  GRB2; growth factor receptor-bound protein 2 [KO:K04364]
101036943  SOS1; son of sevenless homolog 1 [KO:K03099]
101046427  SOS2; son of sevenless homolog 2 [KO:K03099]
101047663  HRAS; GTPase HRas isoform X2 [KO:K02833]
101047035  KRAS; GTPase KRas isoform X1 [KO:K07827]
101036877  NRAS; GTPase NRas [KO:K07828]
101043605  ARAF; serine/threonine-protein kinase A-Raf [KO:K08845] [EC:2.7.11.1]
101052142  BRAF; serine/threonine-protein kinase B-raf isoform X2 [KO:K04365] [EC:2.7.11.1]
101054052  RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X2 [KO:K04366] [EC:2.7.11.1]
101033901  MICB; MHC class I polypeptide-related sequence B [KO:K07985]
101028387  MHC class I polypeptide-related sequence A-like [KO:K07985]
101038332  MHC class I polypeptide-related sequence A-like [KO:K07985]
101042466  NKG2D ligand 3 [KO:K07986]
101043097  NKG2D ligand 3-like [KO:K07986]
101046965  NKG2-D type II integral membrane protein [KO:K06728]
101054319  HCST; LOW QUALITY PROTEIN: hematopoietic cell signal transducer [KO:K07988]
101041583  CD48; CD48 antigen [KO:K06479]
101042633  CD244; natural killer cell receptor 2B4 isoform X1 [KO:K06582]
101045514  PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X4 [KO:K04348] [EC:3.1.3.16]
101035788  PPP3CA; serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101032266  PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
101039659  PPP3R2; calcineurin subunit B type 2 [KO:K06268]
104650539  PPP3R1; calcineurin subunit B type 1 [KO:K06268]
101049490  NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
101046010  PRKCA; protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
101039384  PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
101032613  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
101045348  SH2D1B; SH2 domain-containing protein 1B [KO:K07989]
101034639  SH2D1A; SH2 domain-containing protein 1A [KO:K07990]
101054160  IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]
101050965  IFNGR2; interferon gamma receptor 2 [KO:K05133]
101032308  interferon alpha-8-like [KO:K05414]
101032622  interferon alpha-2-like [KO:K05414]
101032943  IFNA13; interferon alpha-1/13 [KO:K05414]
104649849  interferon alpha-5-like [KO:K05414]
101034105  interferon alpha-8-like [KO:K05414]
101034416  interferon alpha-5-like [KO:K05414]
101034728  IFNA21; interferon alpha-21 [KO:K05414]
101035681  IFNB1; interferon beta [KO:K05415]
101035044  IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]
101030281  TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]
101045196  TNFRSF10A; tumor necrosis factor receptor superfamily member 10A isoform X1 [KO:K04722]
101042934  TNFRSF10B; tumor necrosis factor receptor superfamily member 10B [KO:K04722]
101035660  FASLG; tumor necrosis factor ligand superfamily member 6 isoform X1 [KO:K04389]
101035635  FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]
101039443  GZMB; granzyme B [KO:K01353] [EC:3.4.21.79]
101039918  PRF1; perforin-1 [KO:K07818]
101029697  CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]
101040331  BID; BH3-interacting domain death agonist [KO:K04726]
101043423  RAET1E; LOW QUALITY PROTEIN: NKG2D ligand 4 [KO:K07987]
101037366  NKG2D ligand 2-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
sbq04010  MAPK signaling pathway
sbq04020  Calcium signaling pathway
sbq04060  Cytokine-cytokine receptor interaction
sbq04210  Apoptosis
sbq04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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