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Gene expression profiling demonstrates that TGF-β1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-β signaling

descriptionPublicationkeyboard_double_arrow_right Article 11 May 2005 English Publisher:American Physiological SocietyJournal:Physiological Genomics, volume 21, pages 396-403 (issn: 1094-8341, eissn: 1531-2267,

Authors: Snorri S. Thorgeirsson; Stefan Karlsson; Jonas Larsson; Marie-José Goumans; Göran Karlsson; Ju Seog Lee; Yingchun Liu; +1 Authors

doi: 10.1152/physiolgenomics.00303.2004

pmid: 15769904

Gene expression profiling demonstrates that TGF-β1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-β signaling

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Abstract

Transforming growth factor-β1 (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 (TβRII) 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 TβRII/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.

Related Organizations

Lund University
Sweden
National Cancer Institute
United States

Keywords

Reverse Transcriptase Polymerase Chain Reaction, Receptor, Transforming Growth Factor-beta Type I, Fibroblasts, Protein Serine-Threonine Kinases, Embryo, Mammalian, Transforming Growth Factor beta1, Mice, Gene Expression Regulation, Transforming Growth Factor beta, Animals, Humans, Activin Receptors, Type I, Receptors, Transforming Growth Factor beta, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Signal Transduction

6 Research products, page 1 of 1

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