TNF-alpha and mucus production in lung epythelium (Rattus norvegicus)

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1LPSBDRELung epithel cellMucine 2/5ACIL6ProteasomeNucleusRasTgfaEGFRRafIKKbpp90 rskTNFR1Shcp65Nemop50TraddRipk2Sp1SOSNF-kBMuc5acMEKMuc2p50Grb2NF-kBIKKaMuc2p65IKBaTlr4Muc5acERKTraf2TnfaIl6


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.

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  1. 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


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87777view11:07, 25 July 2016MirellaKalafatiOntology Term : 'signaling pathway' added !
82987view00:40, 17 November 2015Mkutmonfixed unconnected lines
82977view23:47, 16 November 2015Mkutmonfixed outdated identifiers
58946view18:07, 21 February 2013MaintBotUpdated Ensembl data source
41692view02:36, 2 March 2011MaintBotRemoved redundant pathway information and comments
36248view01:02, 12 March 2010KhanspersModified categories
36152view14:54, 3 March 2010Julia139Modified description
36151view14:51, 3 March 2010Julia139Modified description
36150view14:49, 3 March 2010Julia139Periodical save, work in progress
36149view14:37, 3 March 2010Julia139New pathway

External references


View all...
NameTypeDatabase referenceComment
EGFRGeneProduct24329 (Entrez Gene)
ERKGeneProduct116590 (Entrez Gene)
Grb2GeneProduct81504 (Entrez Gene)
IKBaGeneProductENSRNOG00000007390 (Ensembl)
IKKaGeneProduct309361 (Entrez Gene)
IKKbGeneProduct84351 (Entrez Gene)
Il6GeneProduct24498 (Entrez Gene)
MEKGeneProduct170851 (Entrez Gene)
Muc2GeneProduct24572 (Entrez Gene)
Muc5acGeneProductENSRNOG00000058420 (Ensembl)
NF-kBGeneProduct81736 (Entrez Gene)
NemoGeneProduct309295 (Entrez Gene)
RafGeneProduct24703 (Entrez Gene)
RasGeneProductPF00071 (Pfam)
Ripk2GeneProduct362491 (Entrez Gene)
SOSGeneProduct313845 (Entrez Gene)
ShcGeneProduct85385 (Entrez Gene)
Sp1GeneProduct24790 (Entrez Gene)
TNFR1GeneProduct25625 (Entrez Gene)
TgfaGeneProduct24827 (Entrez Gene)
Tlr4GeneProduct29260 (Entrez Gene)
TnfaGeneProduct24835 (Entrez Gene)
TraddGeneProduct246756 (Entrez Gene)
Traf2GeneProduct311786 (Entrez Gene)
p50GeneProduct81736 (Entrez Gene)
p65GeneProduct309165 (Entrez Gene)
pp90 rskGeneProduct117269 (Entrez Gene)

Annotated Interactions

No annotated interactions

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