KEGG   PATHWAY: aju04650
Entry
aju04650                    Pathway                                
Name
Natural killer cell mediated cytotoxicity - Acinonyx jubatus (cheetah)
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
aju04650  Natural killer cell mediated cytotoxicity
aju04650

Other DBs
GO: 0042267
Organism
Acinonyx jubatus (cheetah) [GN:aju]
Gene
106980871  LOW QUALITY PROTEIN: killer cell immunoglobulin-like receptor 3DL3 [KO:K07980]
106965691  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
106965688  uncharacterized protein LOC106965688 [KO:K06541]
106965692  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
113597883  NKG2-A/NKG2-B type II integral membrane protein-like isoform X1 [KO:K06541]
106965694  NKG2-F type II integral membrane protein-like isoform X1 [KO:K06541]
106965690  NKG2-A/NKG2-B type II integral membrane protein-like isoform X2 [KO:K06541]
106965693  NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]
106965721  natural killer cells antigen CD94 isoform X1 [KO:K06516]
106965341  tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]
106982085  tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]
106988776  tyrosine-protein phosphatase non-receptor type 11-like isoform X1 [KO:K07293] [EC:3.1.3.48]
106980319  intercellular adhesion molecule 1 isoform X1 [KO:K06490]
106978698  intercellular adhesion molecule 2 isoform X1 [KO:K06523]
106979092  integrin alpha-L isoform X3 [KO:K05718]
106985666  integrin beta-2 [KO:K06464]
106973108  protein-tyrosine kinase 2-beta isoform X2 [KO:K05871] [EC:2.7.10.2]
106970805  proto-oncogene vav isoform X1 [KO:K05730]
106988256  guanine nucleotide exchange factor VAV2 isoform X2 [KO:K05730]
106974247  guanine nucleotide exchange factor VAV3 [KO:K05730]
106982604  ras-related C3 botulinum toxin substrate 1 isoform X2 [KO:K04392]
106981077  ras-related C3 botulinum toxin substrate 2 isoform X1 [KO:K07860]
106986311  ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]
106976449  serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]
106980282  dual specificity mitogen-activated protein kinase kinase 1 isoform X2 [KO:K04368] [EC:2.7.12.2]
106975474  dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]
106969232  mitogen-activated protein kinase 3 isoform X2 [KO:K04371] [EC:2.7.11.24]
106990008  mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]
106983958  tumor necrosis factor [KO:K03156]
106970701  granulocyte-macrophage colony-stimulating factor [KO:K05427]
106966359  interferon gamma [KO:K04687]
106985421  natural cytotoxicity triggering receptor 2 [KO:K06742]
106974710  TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]
106982436  tyrosine-protein kinase Lck isoform X2 [KO:K05856] [EC:2.7.10.2]
106986773  low affinity immunoglobulin gamma Fc region receptor III-A isoform X1 [KO:K06463]
106980911  LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 1 [KO:K06741]
106983985  natural cytotoxicity triggering receptor 3 isoform X1 [KO:K06743]
106978536  high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]
106966220  T-cell surface glycoprotein CD3 zeta chain isoform X1 [KO:K06453]
106976677  tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]
106976132  tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]
106973445  lymphocyte cytosolic protein 2 [KO:K07361]
106966176  linker for activation of T-cells family member 1 isoform X1 [KO:K07362]
106977524  linker for activation of T-cells family member 2 isoform X1 [KO:K26356]
106974495  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 isoform X1 [KO:K01116] [EC:3.1.4.11]
106984018  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 isoform X1 [KO:K05859] [EC:3.1.4.11]
106978835  SH3 domain-binding protein 2 isoform X2 [KO:K07984]
106984896  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106984265  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]
106973880  phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]
106976917  phosphatidylinositol 3-kinase regulatory subunit alpha isoform X2 [KO:K02649]
106973297  LOW QUALITY PROTEIN: phosphatidylinositol 3-kinase regulatory subunit gamma [KO:K02649]
106969150  phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]
106968910  tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]
106988382  SHC-transforming protein 1 isoform X1 [KO:K06279]
106978092  SHC-transforming protein 2 isoform X1 [KO:K17447]
106987970  SHC-transforming protein 3 [KO:K17448]
106967221  SHC-transforming protein 4 isoform X1 [KO:K17449]
106987795  growth factor receptor-bound protein 2 isoform X1 [KO:K04364]
106978987  son of sevenless homolog 1 isoform X1 [KO:K03099]
106989073  son of sevenless homolog 2 isoform X1 [KO:K03099]
106987957  GTPase HRas isoform X1 [KO:K02833]
106968778  GTPase KRas isoform X1 [KO:K07827]
106969596  GTPase NRas [KO:K07828]
106972677  serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]
106970441  serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]
106977129  RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]
106989404  UL16-binding protein 1-like isoform X1 [KO:K07986]
106965687  NKG2-D type II integral membrane protein isoform X2 [KO:K06728]
106974718  hematopoietic cell signal transducer [KO:K07988]
106978526  CD48 antigen [KO:K06479]
106978528  natural killer cell receptor 2B4 isoform X2 [KO:K06582]
106970974  serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
106982482  protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]
106981120  serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]
106967692  calcineurin subunit B type 1 [KO:K06268]
106972076  calcineurin subunit B type 2 [KO:K06268]
106977679  nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]
106980384  nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]
106975306  protein kinase C alpha type isoform X1 [KO:K02677] [EC:2.7.11.13]
106970449  protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]
106980855  protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]
106986768  SH2 domain-containing protein 1B [KO:K07989]
106972834  SH2 domain-containing protein 1A isoform X2 [KO:K07990]
106985768  interferon gamma receptor 1 [KO:K05132]
106966456  interferon gamma receptor 2 [KO:K05133]
128312015  interferon alpha-like [KO:K05414]
128312017  interferon beta-like [KO:K05414]
128312193  interferon alpha-like [KO:K05414]
106971015  interferon alpha-like [KO:K05414]
106971043  interferon alpha-2-like [KO:K05414]
106971134  interferon alpha [KO:K05414]
106989747  interferon alpha [KO:K05414]
106971145  interferon beta [KO:K05415]
106966457  interferon alpha/beta receptor 1 isoform X1 [KO:K05130]
106966459  interferon alpha/beta receptor 2 isoform X1 [KO:K05131]
106990055  tumor necrosis factor ligand superfamily member 10 [KO:K04721]
106982854  tumor necrosis factor receptor superfamily member 10B-like isoform X1 [KO:K04722]
106979842  tumor necrosis factor ligand superfamily member 6 [KO:K04389]
106980953  tumor necrosis factor receptor superfamily member 6 isoform X1 [KO:K04390]
106987873  mast cell protease 1A-like isoform X1 [KO:K01353] [EC:3.4.21.79]
106987852  granzyme B(G,H)-like [KO:K01353] [EC:3.4.21.79]
106967198  perforin-1 [KO:K07818]
106979326  caspase-3 isoform X3 [KO:K02187] [EC:3.4.22.56]
106968455  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
aju04010  MAPK signaling pathway
aju04020  Calcium signaling pathway
aju04060  Cytokine-cytokine receptor interaction
aju04210  Apoptosis
aju04630  JAK-STAT signaling pathway
KO pathway
ko04650   
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