Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice.
Disruption of the adaptor protein ELF, a beta-spectrin, leads to disruption of transforming growth factor-beta (TGF-beta) signaling by Smad proteins in mice. Elf-/- mice exhibit a phenotype similar to smad2+/-/smad3+/- mutant mice of midgestational death due to gastrointestinal, liver, neural, and heart defects. We show that TGF-beta triggers phosphorylation and association of ELF with Smad3 and Smad4, followed by nuclear translocation. ELF deficiency results in mislocalization of Smad3 and Smad4 and loss of the TGF-beta-dependent transcriptional response, which could be rescued by overexpression of the COOH-terminal region of ELF. This study reveals an unexpected molecular link between a major dynamic scaffolding protein and a key signaling pathway.
Pubmed ID: 12543979 RIS Download
Abnormalities, Multiple | Animals | Carrier Proteins | Cell Membrane | Cell Nucleus | Contractile Proteins | DNA-Binding Proteins | Embryonic and Fetal Development | Filamins | Gene Targeting | Genes, fos | Liver | Mice | Mice, Knockout | Microfilament Proteins | Microscopy, Confocal | Mutation | Phenotype | Phosphorylation | Platelet-Derived Growth Factor | Signal Transduction | Smad2 Protein | Smad3 Protein | Smad4 Protein | Spectrin | Trans-Activators | Transcriptional Activation | Transforming Growth Factor beta | Tumor Cells, Cultured