Disruption of transforming growth factor-β signaling in ELF β-spectrin-deficient mice

Y Tang, V Katuri, A Dillner, B Mishra, CX Deng… - Science, 2003 - science.org
Y Tang, V Katuri, A Dillner, B Mishra, CX Deng, L Mishra
Science, 2003science.org
Disruption of the adaptor protein ELF, a β-spectrin, leads to disruption of transforming growth
factor–β (TGF-β) 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-β 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-β–dependent transcriptional …
Disruption of the adaptor protein ELF, a β-spectrin, leads to disruption of transforming growth factor–β (TGF-β) signaling by Smad proteins in mice. Elf −/− mice exhibit a phenotype similar tosmad2 +/−/smad3 +/−mutant mice of midgestational death due to gastrointestinal, liver, neural, and heart defects. We show that TGF-β 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-β–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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