KEGG PATHWAY: ppam04650

KEGG

PATHWAY: ppam04650

Entry

ppam04650                   Pathway

Name

Natural killer cell mediated cytotoxicity - Pteronotus mesoamericanus (Parnell's mustached bat)

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

Natural killer cell mediated cytotoxicity

Other DBs

GO:

Organism

Pteronotus mesoamericanus (Parnell's mustached bat) [GN:ppam]

Gene

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

NKG2-A/NKG2-B type II integral membrane protein-like [KO:K06541]

natural killer cells antigen CD94-like [KO:K06516]

natural killer cells antigen CD94-like [KO:K06516]

PTPN6; tyrosine-protein phosphatase non-receptor type 6 isoform X1 [KO:K05697] [EC:3.1.3.48]

PTPN11; tyrosine-protein phosphatase non-receptor type 11 isoform X1 [KO:K07293] [EC:3.1.3.48]

ICAM1; intercellular adhesion molecule 1 isoform X1 [KO:K06490]

ICAM2; intercellular adhesion molecule 2 [KO:K06523]

ITGAL; integrin alpha-L isoform X1 [KO:K05718]

ITGB2; integrin beta-2 [KO:K06464]

PTK2B; protein-tyrosine kinase 2-beta [KO:K05871] [EC:2.7.10.2]

VAV3; guanine nucleotide exchange factor VAV3 [KO:K05730]

VAV2; guanine nucleotide exchange factor VAV2 isoform X1 [KO:K05730]

VAV1; proto-oncogene vav isoform X1 [KO:K05730]

ras-related C3 botulinum toxin substrate 1-like [KO:K04392]

RAC1; ras-related C3 botulinum toxin substrate 1 isoform X1 [KO:K04392]

RAC2; ras-related C3 botulinum toxin substrate 2 [KO:K07860]

RAC3; ras-related C3 botulinum toxin substrate 3 isoform X1 [KO:K07861]

PAK1; serine/threonine-protein kinase PAK 1 [KO:K04409] [EC:2.7.11.1]

MAP2K1; dual specificity mitogen-activated protein kinase kinase 1 [KO:K04368] [EC:2.7.12.2]

MAP2K2; dual specificity mitogen-activated protein kinase kinase 2 [KO:K04369] [EC:2.7.12.2]

MAPK3; mitogen-activated protein kinase 3 [KO:K04371] [EC:2.7.11.24]

MAPK1; mitogen-activated protein kinase 1 [KO:K04371] [EC:2.7.11.24]

TNF; tumor necrosis factor [KO:K03156]

CSF2; granulocyte-macrophage colony-stimulating factor [KO:K05427]

IFNG; interferon gamma [KO:K04687]

putative killer cell immunoglobulin-like receptor like protein KIR3DP1 [KO:K07982]

TYROBP; TYRO protein tyrosine kinase-binding protein isoform X1 [KO:K07992]

LCK; tyrosine-protein kinase Lck [KO:K05856] [EC:2.7.10.2]

Ig heavy chain Mem5-like [KO:K06856]

low affinity immunoglobulin gamma Fc region receptor III-A-like isoform X1 [KO:K06463]

LOW QUALITY PROTEIN: natural cytotoxicity triggering receptor 1-like [KO:K06741]

NCR3; natural cytotoxicity triggering receptor 3 [KO:K06743]

FCER1G; high affinity immunoglobulin epsilon receptor subunit gamma [KO:K07983]

CD247; T-cell surface glycoprotein CD3 zeta chain [KO:K06453]

tyrosine-protein kinase ZAP-70 isoform X1 [KO:K07360] [EC:2.7.10.2]

SYK; tyrosine-protein kinase SYK isoform X1 [KO:K05855] [EC:2.7.10.2]

LCP2; lymphocyte cytosolic protein 2 [KO:K07361]

LAT; linker for activation of T-cells family member 1 [KO:K07362]

LAT2; linker for activation of T-cells family member 2 isoform X1 [KO:K26356]

PLCG1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 [KO:K01116] [EC:3.1.4.11]

PLCG2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-2 [KO:K05859] [EC:3.1.4.11]

SH3BP2; SH3 domain-binding protein 2 [KO:K07984]

PIK3CD; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X1 [KO:K00922] [EC:2.7.1.153]

PIK3CA; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [KO:K00922] [EC:2.7.1.153]

PIK3CB; phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform [KO:K00922] [EC:2.7.1.153]

PIK3R2; phosphatidylinositol 3-kinase regulatory subunit beta [KO:K02649]

PIK3R3; phosphatidylinositol 3-kinase regulatory subunit gamma isoform X1 [KO:K02649]

PIK3R1; phosphatidylinositol 3-kinase regulatory subunit alpha isoform X1 [KO:K02649]

FYN; tyrosine-protein kinase Fyn isoform X1 [KO:K05703] [EC:2.7.10.2]

SHC1; SHC-transforming protein 1 [KO:K06279]

SHC2; SHC-transforming protein 2 [KO:K17447]

SHC3; SHC-transforming protein 3 [KO:K17448]

SHC4; SHC-transforming protein 4 [KO:K17449]

GRB2; growth factor receptor-bound protein 2 [KO:K04364]

son of sevenless homolog 2 isoform X1 [KO:K03099]

SOS1; son of sevenless homolog 1 isoform X1 [KO:K03099]

HRAS; GTPase HRas isoform X1 [KO:K02833]

KRAS; GTPase KRas isoform X1 [KO:K07827]

NRAS; GTPase NRas [KO:K07828]

ARAF; serine/threonine-protein kinase A-Raf isoform X1 [KO:K08845] [EC:2.7.11.1]

BRAF; serine/threonine-protein kinase B-raf isoform X1 [KO:K04365] [EC:2.7.11.1]

RAF1; RAF proto-oncogene serine/threonine-protein kinase isoform X1 [KO:K04366] [EC:2.7.11.1]

uncharacterized protein LOC129067841 [KO:K07986]

NKG2-D type II integral membrane protein-like [KO:K06728]

NKG2-D type II integral membrane protein-like [KO:K06728]

HCST; hematopoietic cell signal transducer isoform X1 [KO:K07988]

CD48; CD48 antigen [KO:K06479]

CD244; natural killer cell receptor 2B4 [KO:K06582]

PPP3CC; serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform isoform X1 [KO:K04348] [EC:3.1.3.16]

PPP3CB; serine/threonine-protein phosphatase 2B catalytic subunit beta isoform isoform X1 [KO:K04348] [EC:3.1.3.16]

PPP3CA; protein phosphatase 3 catalytic subunit alpha isoform X1 [KO:K04348] [EC:3.1.3.16]

PPP3R2; calcineurin subunit B type 2 [KO:K06268]

PPP3R1; calcineurin subunit B type 1 [KO:K06268]

NFATC1; nuclear factor of activated T-cells, cytoplasmic 1 isoform X1 [KO:K04446]

NFATC2; nuclear factor of activated T-cells, cytoplasmic 2 isoform X1 [KO:K17332]

PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]

PRKCB; protein kinase C beta type isoform X1 [KO:K19662] [EC:2.7.11.13]

PRKCG; protein kinase C gamma type isoform X1 [KO:K19663] [EC:2.7.11.13]

SH2D1B; SH2 domain-containing protein 1B [KO:K07989]

SH2D1A; SH2 domain-containing protein 1A isoform X1 [KO:K07990]

IFNGR1; interferon gamma receptor 1 isoform X1 [KO:K05132]

IFNGR2; interferon gamma receptor 2 [KO:K05133]

LOW QUALITY PROTEIN: interferon alpha-4-like [KO:K05414]

IFNB1; interferon beta [KO:K05415]

IFNAR1; interferon alpha/beta receptor 1 [KO:K05130]

IFNAR2; interferon alpha/beta receptor 2 isoform X1 [KO:K05131]

TNFSF10; tumor necrosis factor ligand superfamily member 10 [KO:K04721]

tumor necrosis factor receptor superfamily member 1A-like [KO:K04722]

tumor necrosis factor receptor superfamily member 10B-like [KO:K04722]

FASLG; tumor necrosis factor ligand superfamily member 6 [KO:K04389]

FAS; tumor necrosis factor receptor superfamily member 6 [KO:K04390]

LOW QUALITY PROTEIN: granzyme H-like [KO:K01353] [EC:3.4.21.79]

granzyme B-like [KO:K01353] [EC:3.4.21.79]

PRF1; perforin-1 [KO:K07818]

CASP3; caspase-3 isoform X1 [KO:K02187] [EC:3.4.22.56]

BID; BH3-interacting domain death agonist [KO:K04726]

retinoic acid early transcript 1E-like [KO:K07987]

Compound

Calcium cation

Diacylglycerol

D-myo-Inositol 1,4,5-trisphosphate

Phosphatidylinositol-3,4,5-trisphosphate

Reference

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

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

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

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

Authors

Perussia B.

Title

Signaling for cytotoxicity.

Journal

Nat Immunol 1:372-4 (2000)
DOI:10.1038/80808

Reference

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

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

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

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

Authors

Bonnema JD, Leibson PJ.

Title

Signal transduction during NK cell activation.

Journal

Chem Immunol 64:28-43 (1996)

Reference

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

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

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

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

Authors

Blott EJ, Griffiths GM.

Title

Secretory lysosomes.

Journal

Nat Rev Mol Cell Biol 3:122-31 (2002)
DOI:10.1038/nrm732

Reference

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

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

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

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

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

MAPK signaling pathway

Calcium signaling pathway

Cytokine-cytokine receptor interaction

Apoptosis

JAK-STAT signaling pathway

KO pathway

LinkDB

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