Gene expression profiling demonstrates that TGF-beta1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-beta signaling.
Transforming growth factor-beta1 (TGF-beta) regulates cellular functions like proliferation, differentiation, and apoptosis. On the cell surface, TGF-beta binds to receptor complexes consisting of TGF-beta receptor type II (TbetaRII) 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 TbetaRII/Alk5 can be relevant for TGF-beta signaling. We have screened for alternative receptors for TGF-beta and also for gene targets of TGF-beta signaling, by performing functional assays and microarray analysis in murine embryonic fibroblast (MEF) cell lines lacking Alk5. Data from TGF-beta-stimulated Alk5(-/-) cells show them to be completely unaffected by TGF-beta. Additionally, 465 downstream targets of Alk5 signaling were identified when comparing Alk5(-/-) or TGF-beta-stimulated Alk5(+/+) MEFs with unstimulated Alk5(+/+) cells. Our results demonstrate that, in MEFs, TGF-beta signals exclusively through complexes involving Alk5, and give insight to its downstream effector genes.
Karlsson
Göran
G
Department of Molecular Medicine and Gene Therapy, Institute of Laboratory Medicine, Lund, Sweden.
Liu
Yingchun
Y
Larsson
Jonas
J
Goumans
Marie-José
MJ
Lee
Ju-Seog
JS
Thorgeirsson
Snorri S
SS
Ringnér
Markus
M
Karlsson
Stefan
S
D030201:Activin Receptors, Type I / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology*; D053773:Transforming Growth Factor beta1
D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; C508961:Tgfb1 protein, mouse; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D017346:Protein Serine-Threonine Kinases; D030201:Activin Receptors, Type I; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human; C000625842:Tgfbr1 protein, mouse