Göran Karlsson, Yingchun Liu, Jonas Larsson, Mari-José Goumans, Ju-Seog Lee, Snorri S. Thorgeirsson, Markus Ringnér and Stefan Karlsson
Gene expression profiling demonstrates that TGF-β1 signals exclusively through receptor complexes involving Alk5 and identifies targets of TGF-β signaling
Physiological Genomics 21, 396-403 (2005)
Transforming growth factor beta 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 (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 besides 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.
LU TP 04-33