TNF Stress Related Signaling Pathway

Preferred Label : TNF Stress Related Signaling Pathway;

NCIt related terms : TNF/Stress Related Signaling;

Alternative definition : BIOCARTA: TNF acts on several different signaling pathways through two cell surface receptors, TNFR1 and TNFR2 to regulate apoptotic pathways, NF-kB activation of inflammation, and activate stress-activated protein kinases (SAPKs). Interaction of TNFR1 with TRADD leads to activation of NF-kB and apoptosis pathways, while interaction with TRAF2 has generally been thought to be involved in stress kinase and NF-kB activation but is not required for TNF to induce apoptosis. Activation of NF-kB is mediated by TRAF2 through the NIK kinase and also by RIP but the observation that TNF activates NF-kB in mice lacking TRAF2 indicates that TRAF-2 does not play an essential role in this process. Stress-activated protein kinases, also called JNKs, are a family of map kinases activated by cellular stress and inflammatory signals. Binding of TNF to the TNFR1 receptor activates the germinal center kinase (GCK) through the TNF adaptor Traf2, activating the map kinase MEKK1. Both GCK and MEKK1 interact with Traf2, and GCK is required for MEKK1 activation by TNF, but GCK kinase activity does not appear to be required for MEKK1 activation. Instead, GCK activates MEKK1 by causing MEKK1 oligomerization and autophosphorylation. Tank increases the affinity of Traf2 for GCK to increase Map kinase activation by TNF. Once activated, MEKK1 stands at the top of a map kinase pathway leading to transcriptional regulation, including JNK phosphorylation of c-Jun to stimulate transcriptional activation by AP-1, a heterodimer of c-jun and fos or ATF proteins. The activation of the p38 Map kinase also contributes to AP-1 activation leading to the transcriptional activation of many stress and growth related genes. RIP has been suggested as a component of the p38 pathway in addition to playing a role in NF-kB activation. MEKK1 knockout mice support the role of MEKK1 in JNK activation in some cells but did not support MEKK1 dependent activation of NF-kB. Alternative redundant mechanisms may obscure the role of MEKK1 in NF-kB mechanisms. TNF activation of stress kinase pathways and downstream transcription factors may help to modulate the apoptotic pathways also activated by TNF. (This definition may be outdated - see the DesignNote.);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_stressPathway;

Details

Origin ID

C39241;

UMLS CUI

C1515167;

Semantic type(s)
- Cell Function [UMLS semantic type]
has_gene_product_element
- Caspase-2 [NCIt concept]
- Cyclic AMP-Dependent Transcription Factor ATF-1 [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Alpha [NCIt concept]
- Inhibitor of Nuclear Factor Kappa-B Kinase Subunit Beta [NCIt concept]
- Mitogen-Activated Protein Kinase 14 [NCIt concept]
- Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 [NCIt concept]
- Receptor-Interacting Serine/Threonine-Protein Kinase 1 [NCIt concept]
- TRAF Family Member-Associated NF-Kappa-B Activator [NCIt concept]
- Tumor Necrosis Factor [NCIt concept]
- Tumor Necrosis Factor Receptor 1-Associated DEATH Domain Protein [NCIt concept]
pathway_has_gene_element
- ATF1 wt Allele [NCIt concept]
- CASP2 wt Allele [NCIt concept]
- CHUK wt Allele [NCIt concept]
- IKBKB wt Allele [NCIt concept]
- MAP4K4 wt Allele [NCIt concept]
- MAPK14 wt Allele [NCIt concept]
- RIPK1 wt Allele [NCIt concept]
- TANK wt Allele [NCIt concept]
- TNF wt Allele [NCIt concept]
- TRADD wt Allele [NCIt concept]

Keyword's position in hierarchy(ies) :

You can consult :

recommendations
documents concerning education
documents for patients