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Disruption of Transforming Growth Factor-β Signaling in ELF β-Spectrin-Deficient Mice

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Science  24 Jan 2003:
Vol. 299, Issue 5606, pp. 574-577
DOI: 10.1126/science.1075994

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Abstract

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.

  • * To whom correspondence should be addressed. E-mail: lm229{at}georgetown.edu and lopamishra{at}yahoo.com

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