Transforming Growth Factor {beta} Can Stimulate Smad1 Phosphorylation Independently of Bone Morphogenic Protein Receptors.
Transforming growth factor-beta (TGFbeta) superfamily ligands control a diverse set of cellular processes by activating type I and type II serine-threonine receptor kinases. Canonical TGFbeta signaling is mediated via the TbetaRI/ALK5 type I receptor that phosphorylates Smad2 and Smad3 in their SXS motif to facilitate their activation and subsequent role in transcriptional regulation. Canonical bone morphogenic protein (BMP) signaling is mediated via the ALK1/2/3/6 type I receptors that phosphorylate Smad1, Smad5, and Smad8 in their SXS motif. However, studies in endothelial cells have shown that TGFbeta can also lead to the phosphorylation of Smad1, dependent on ALK1 receptor activity. Here we present data showing that TGFbeta can significantly induce Smad1 phosphorylation in several non-endothelial cell lineages. Additionally, by using chemical inhibitors specific for the TGFbeta/activin/nodal (ALK4/5/7) and BMP (ALK1/2/3/6) type I receptors, we show that in some cell types TGFbeta induces Smad1 phosphorylation independently of the BMP type I receptors. Thus, TGFbeta-mediated Smad1 phosphorylation appears to occur via different receptor complexes in a cell type-specific manner.
Wrighton
Katharine H
KH
Michael E. DeBakey Department of Surgery and Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
Lin
Xia
X
Yu
Paul B
PB
Feng
Xin-Hua
XH
D020816:Amino Acid Motifs; D000818:Animals; D052004:Bone Morphogenetic Protein Receptors / Q000378:metabolism*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008024:Ligands; D051379:Mice; D008954:Models, Biological; D010766:Phosphorylation; D015398:Signal Transduction; D051898:Smad1 Protein / Q000378:metabolism*; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D008024:Ligands; D051898:Smad1 Protein; D016212:Transforming Growth Factor beta; D052004:Bone Morphogenetic Protein Receptors