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Published on: September 9, 2010
Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice
Yi Tang1, Varalakshmi Katuri, Allan Dillner
1Laboratory of Developmental Biology, Department of Medicine, Georgetown University, Washington, DC 20007, USA.
Abstract:
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.
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