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Gene expression profiling demonstrates that TGF-{beta}1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-{beta} signaling.

Karlsson, Göran LU ; Liu, Yingchun LU ; Larsson, Jonas LU ; Goumans, Marie-Jose; Lee, Ju-Seog; Thorgeirsson, Snorri S; Ringnér, Markus LU and Karlsson, Stefan LU (2005) In Physiological Genomics 21(3). p.396-403
Abstract
Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show... (More)
Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-β-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
signal transduction, Smad, microarrays
in
Physiological Genomics
volume
21
issue
3
pages
396 - 403
publisher
American Physiological Society
external identifiers
  • wos:000229021500013
  • pmid:15769904
  • scopus:21244489290
ISSN
1094-8341
DOI
10.1152/physiolgenomics.00303.2004
language
English
LU publication?
yes
id
6f7d20f4-c646-4fb0-b086-a32f176797cd (old id 134937)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15769904&dopt=Abstract
date added to LUP
2007-07-11 12:19:08
date last changed
2017-01-29 03:23:06
@article{6f7d20f4-c646-4fb0-b086-a32f176797cd,
  abstract     = {Transforming growth factor-β 1 (TGF-β) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-β binds to receptor complexes consisting of TGF-β receptor type II (Tβ RII) and activin-like kinase receptor-5 (Alk5), and the downstream signaling is transduced by Smad and MAPK proteins. Recent data have shown that alternative receptor combinations aside from the classical pairing of Tβ RII/Alk5 can be relevant for TGF-β signaling. We have screened for alternative receptors for TGF-β and also for gene targets of TGF-β signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-β-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-β. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-β-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-β signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.},
  author       = {Karlsson, Göran and Liu, Yingchun and Larsson, Jonas and Goumans, Marie-Jose and Lee, Ju-Seog and Thorgeirsson, Snorri S and Ringnér, Markus and Karlsson, Stefan},
  issn         = {1094-8341},
  keyword      = {signal transduction,Smad,microarrays},
  language     = {eng},
  number       = {3},
  pages        = {396--403},
  publisher    = {American Physiological Society},
  series       = {Physiological Genomics},
  title        = {Gene expression profiling demonstrates that TGF-{beta}1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-{beta} signaling.},
  url          = {http://dx.doi.org/10.1152/physiolgenomics.00303.2004},
  volume       = {21},
  year         = {2005},
}