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.
Mesh Terms:
Abnormalities, Multiple, Animals, Carrier Proteins, Cell Membrane, Cell Nucleus, Contractile Proteins, DNA-Binding Proteins, Embryonic and Fetal Development, 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
Abnormalities, Multiple, Animals, Carrier Proteins, Cell Membrane, Cell Nucleus, Contractile Proteins, DNA-Binding Proteins, Embryonic and Fetal Development, 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
Science
Date: Jan. 24, 2003
PubMed ID: 12543979
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