Ras-Independent Cell-Mediated Cytotoxicity Pathway

Preferred Label : Ras-Independent Cell-Mediated Cytotoxicity Pathway;

NCIt related terms : Ras-Independent pathway in NK cell-mediated cytotoxicity;

Alternative definition : BIOCARTA: NK (natural killer) cells are lymphocytes distinct from B and T cells that induce perforin-mediated lysis of tumor cells and virus-infected cells. NK cell-mediated cytotoxicity is activated by glycoproteins on the cell surface (activating receptors) and inhibited by MHC-1 with self-peptide bound. The MHC-1 inhibitory signal through Ig-family or lectin receptors prevents NK cells from killing normal cells. Abnormal MHC-1 expression in infected or tumor cells results in the release of perforin, the lysis of the abnormal cell and the release of cytokines that stimulate the immune response. MAP kinase inhibitors, but not ras inhibitors, are able to block NK cell cytotoxicity, indicating that the pathway can function by a ras-independent manner that involves the MAP kinase pathway. This pathway includes phosphoinositide-3-kinase (PI3K) as a key component, followed by Rac1 and the exchange factor Vav. The tyrosine kinase SYK and LAT may provide an additional pathway for activation of MAP kinases leading to NK cell activation, and also Pyk-2 activation by integrins. The protein tyrosine phosphatase SHP-1 appears to mediate the cytotoxicity inhibitory signal that blocks lysis of normal cells. The balance of these positive and negative signaling pathways regulates the role of NK cells in the immune response. (This definition may be outdated - see the DesignNote.);

NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA Definition might be outdated or inaccurate. Please see the Terms and Conditions for Use at http://www.biocarta.com/.;

Biocarta ID : h_nkcellsPathway;

Details

Origin ID

C39165;

UMLS CUI

C1514726;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- Dual Specificity Mitogen-Activated Protein Kinase Kinase 1 [NCIt concept]
- HLA Class I Histocompatibility Antigen, A-2 Alpha Chain [NCIt concept]
- Interleukin-18 [NCIt concept]
- Mitogen-Activated Protein Kinase 3 [NCIt concept]
- NKG2-A/NKG2-B Type II Integral Membrane Protein [NCIt concept]
- NKG2-C Type II Integral Membrane Protein [NCIt concept]
- Natural Killer Cells Antigen CD94 [NCIt concept]
- Phosphatidylinositol 3-Kinase Regulatory Subunit Alpha [NCIt concept]
- Protein-Tyrosine Kinase 2-Beta [NCIt concept]
- Proto-Oncogene Vav [NCIt concept]
- Ras-Related C3 Botulinum Toxin Substrate 1 [NCIt concept]
- Serine/Threonine-Protein Kinase PAK 1 [NCIt concept]
- Tyrosine-Protein Kinase SYK [NCIt concept]
- Tyrosine-Protein Phosphatase Non-Receptor Type 6 [NCIt concept]
pathway_has_gene_element
- HLA-A wt Allele [NCIt concept]
- IL18 wt Allele [NCIt concept]
- KLRC1 wt Allele [NCIt concept]
- KLRC2 wt Allele [NCIt concept]
- KLRD1 wt Allele [NCIt concept]
- MAP2K1 wt Allele [NCIt concept]
- MAPK3 wt Allele [NCIt concept]
- PAK1 wt Allele [NCIt concept]
- PIK3R1 wt Allele [NCIt concept]
- PTK2B wt Allele [NCIt concept]
- PTPN6 wt Allele [NCIt concept]
- RAC1 wt Allele [NCIt concept]
- SYK wt Allele [NCIt concept]
- VAV1 wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

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