Reference - Detail
| RRC ID | 39781 |
|---|---|
| Author | Kusanagi K, Inoue H, Ishidou Y, Mishima HK, Kawabata M, Miyazono K. |
| Title | Characterization of a bone morphogenetic protein-responsive Smad-binding element. |
| Journal | Mol Biol Cell |
| Abstract |
Bone morphogenetic proteins (BMPs) are pleiotropic growth and differentiation factors belonging to the transforming growth factor-beta (TGF-beta) superfamily. Signals of the TGF-beta-like ligands are propagated to the nucleus through specific interaction of transmembrane serine/threonine kinase receptors and Smad proteins. GCCGnCGC has been suggested as a consensus binding sequence for Drosophila Mad regulated by a BMP-like ligand, Decapentaplegic. Smad1 is one of the mammalian Smads activated by BMPs. Here we show that Smad1 binds to this motif upon BMP stimulation in the presence of the common Smad, Smad4. The binding affinity is likely to be relatively low, because Smad1 binds to three copies of the motif weakly, but more repeats of the motif significantly enhance the binding. Heterologous reporter genes (GCCG-Lux) with multiple repeats of the motif respond to BMP stimulation but not to TGF-beta or activin. Mutational analyses reveal several bases critical for the responsiveness. A natural BMP-responsive reporter, pTlx-Lux, is activated by BMP receptors in P19 cells but not in mink lung cells. In contrast, GCCG-Lux responds to BMP stimulation in both cells, suggesting that it is a universal reporter that directly detects Smad phosphorylation by BMP receptors. |
| Volume | 11(2) |
| Pages | 555-65 |
| Published | 2000-2-1 |
| DOI | 10.1091/mbc.11.2.555 |
| PMID | 10679014 |
| PMC | PMC14793 |
| MeSH | Activins Animals Base Sequence Binding Sites Bone Morphogenetic Proteins / pharmacology* Cell Line Consensus Sequence / genetics DNA / genetics DNA / metabolism DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Proteins* Genes, Reporter / genetics Inhibins / pharmacology Insect Proteins / pharmacology Mice Mutation / genetics Recombinant Fusion Proteins / chemistry Recombinant Fusion Proteins / genetics Recombinant Fusion Proteins / metabolism Repetitive Sequences, Nucleic Acid / genetics Response Elements / genetics* Signal Transduction / drug effects Smad Proteins Smad1 Protein Smad4 Protein Trans-Activators / chemistry Trans-Activators / genetics Trans-Activators / metabolism* Transcription Factors* Transcriptional Activation / drug effects* Transforming Growth Factor beta / pharmacology |
| IF | 3.791 |
| Times Cited | 145 |
| WOS Category | CELL BIOLOGY |
| Resource | |
| Human and Animal Cells | 10T1/2(RCB0247) ATDC5(RCB0565) |