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The inflammatory mediator leukotriene D4 induces beta -catenin signaling and its association with anti-apoptotic Bcl-2 in intestinal epithelial cells.

Mezhybovska, Maryna LU ; Wikström, Katarina LU ; Öhd, John LU and Sjölander, Anita LU (2006) In Journal of Biological Chemistry 281(10). p.6776-6784
Abstract
Increased levels of the inflammatory mediator leukotriene D-4 (LTD4) are present at sites of inflammatory bowel disease, and such areas also exhibit an increased risk for subsequent cancer development. It is known that LTD4 affects the expression of many proteins that influence survival and proliferation of intestinal epithelial cells. We demonstrate here that after LTD4 exposure, beta-catenin translocates to the nucleus where it signals activation of the TCF/LEF family of transcription factors. These events are mediated via a phosphatidylinositol 3-kinase-dependent phosphorylation of the inhibitory Ser-9 residue of glycogen synthase kinase 3 beta. We also show that in the presence of LTD4, free beta-catenin translocates to the... (More)
Increased levels of the inflammatory mediator leukotriene D-4 (LTD4) are present at sites of inflammatory bowel disease, and such areas also exhibit an increased risk for subsequent cancer development. It is known that LTD4 affects the expression of many proteins that influence survival and proliferation of intestinal epithelial cells. We demonstrate here that after LTD4 exposure, beta-catenin translocates to the nucleus where it signals activation of the TCF/LEF family of transcription factors. These events are mediated via a phosphatidylinositol 3-kinase-dependent phosphorylation of the inhibitory Ser-9 residue of glycogen synthase kinase 3 beta. We also show that in the presence of LTD4, free beta-catenin translocates to the mitochondria where it associates with the cell survival protein Bcl-2. We hypothesize that LTD4 may enhance cell survival via activation of beta-catenin signaling, in particular, by promoting the association of beta-catenin with Bcl-2 in the mitochondria. Similar to Wnt-1 signaling, LTD4 signals an increased level of free beta-catenin and elevated TCF/LEF promotor activity. This work in intestinal epithelial cells further lends credence to the idea that inflammatory signaling pathways are intrinsically linked with potential oncogenic signals involved in cell survival and apoptosis. (Less)
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type
Contribution to journal
publication status
published
subject
in
Journal of Biological Chemistry
volume
281
issue
10
pages
6776 - 6784
publisher
ASBMB
external identifiers
  • wos:000236030800076
  • pmid:16407243
  • scopus:33646554857
ISSN
1083-351X
DOI
10.1074/jbc.M509999200
language
English
LU publication?
yes
id
6f87ef87-8fcc-477a-96ab-219c127385a4 (old id 150376)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=16407243&dopt=Abstract
date added to LUP
2016-04-01 12:13:49
date last changed
2021-10-06 03:23:52
@article{6f87ef87-8fcc-477a-96ab-219c127385a4,
  abstract     = {Increased levels of the inflammatory mediator leukotriene D-4 (LTD4) are present at sites of inflammatory bowel disease, and such areas also exhibit an increased risk for subsequent cancer development. It is known that LTD4 affects the expression of many proteins that influence survival and proliferation of intestinal epithelial cells. We demonstrate here that after LTD4 exposure, beta-catenin translocates to the nucleus where it signals activation of the TCF/LEF family of transcription factors. These events are mediated via a phosphatidylinositol 3-kinase-dependent phosphorylation of the inhibitory Ser-9 residue of glycogen synthase kinase 3 beta. We also show that in the presence of LTD4, free beta-catenin translocates to the mitochondria where it associates with the cell survival protein Bcl-2. We hypothesize that LTD4 may enhance cell survival via activation of beta-catenin signaling, in particular, by promoting the association of beta-catenin with Bcl-2 in the mitochondria. Similar to Wnt-1 signaling, LTD4 signals an increased level of free beta-catenin and elevated TCF/LEF promotor activity. This work in intestinal epithelial cells further lends credence to the idea that inflammatory signaling pathways are intrinsically linked with potential oncogenic signals involved in cell survival and apoptosis.},
  author       = {Mezhybovska, Maryna and Wikström, Katarina and Öhd, John and Sjölander, Anita},
  issn         = {1083-351X},
  language     = {eng},
  number       = {10},
  pages        = {6776--6784},
  publisher    = {ASBMB},
  series       = {Journal of Biological Chemistry},
  title        = {The inflammatory mediator leukotriene D4 induces beta -catenin signaling and its association with anti-apoptotic Bcl-2 in intestinal epithelial cells.},
  url          = {http://dx.doi.org/10.1074/jbc.M509999200},
  doi          = {10.1074/jbc.M509999200},
  volume       = {281},
  year         = {2006},
}