TNF-alpha and mucus production in lung epythelium (Rattus norvegicus)
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Description
The upregulation of mucine is regulated by three different pathways which result in the activation of NF-kB.
After TNF-alpha activated its receptor and recruited several adaptor proteins, the IKK complex is activated to inhibit IKBa, resulting in the activation and translocation into the nucleus of NF-kB and upregulation of mucine and IL-6. After EGFR activation by TGF-alpha binding, the RAS-MAPK-pp90 RSK pathway leads to inactivation of IKBa and thus to the translocation of NF-kB. Further, pp90 RSK leads to binding of Sp1 transcription factor to its DNA binding site. By activating Tlr4, LPS can inhibit IKBa.
Quality Tags
Ontology Terms
Bibliography
- Lora JM, Zhang DM, Liao SM, Burwell T, King AM, Barker PA, Singh L, Keaveney M, Morgenstern J, Gutierrez-Ramos JC, Coyle AJ, Fraser CC; ''Tumor necrosis factor-alpha triggers mucus production in airway epithelium through an IkappaB kinase beta-dependent mechanism.''; J Biol Chem, 2005 PubMed Europe PMC Scholia
History
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External references
DataNodes
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Name | Type | Database reference | Comment |
---|---|---|---|
EGFR | GeneProduct | 24329 (Entrez Gene) | |
ERK | GeneProduct | 116590 (Entrez Gene) | |
Grb2 | GeneProduct | 81504 (Entrez Gene) | |
IKBa | GeneProduct | ENSRNOG00000007390 (Ensembl) | |
IKKa | GeneProduct | 309361 (Entrez Gene) | |
IKKb | GeneProduct | 84351 (Entrez Gene) | |
Il6 | GeneProduct | 24498 (Entrez Gene) | |
MEK | GeneProduct | 170851 (Entrez Gene) | |
Muc2 | GeneProduct | 24572 (Entrez Gene) | |
Muc5ac | GeneProduct | 682837 (Entrez Gene) | |
NF-kB | GeneProduct | 81736 (Entrez Gene) | |
Nemo | GeneProduct | 309295 (Entrez Gene) | |
Raf | GeneProduct | 24703 (Entrez Gene) | |
Ras | GeneProduct | PF00071 (Pfam) | |
Ripk2 | GeneProduct | 362491 (Entrez Gene) | |
SOS | GeneProduct | 313845 (Entrez Gene) | |
Shc | GeneProduct | 85385 (Entrez Gene) | |
Sp1 | GeneProduct | 24790 (Entrez Gene) | |
TNFR1 | GeneProduct | 25625 (Entrez Gene) | |
Tgfa | GeneProduct | 24827 (Entrez Gene) | |
Tlr4 | GeneProduct | 29260 (Entrez Gene) | |
Tnfa | GeneProduct | 24835 (Entrez Gene) | |
Tradd | GeneProduct | 246756 (Entrez Gene) | |
Traf2 | GeneProduct | 311786 (Entrez Gene) | |
p50 | GeneProduct | 81736 (Entrez Gene) | |
p65 | GeneProduct | 309165 (Entrez Gene) | |
pp90 rsk | GeneProduct | 117269 (Entrez Gene) |
Annotated Interactions
No annotated interactions