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Science. 2003 Jan 24;299(5606):574-7.

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

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  • 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.

PMID:
12543979
[PubMed - indexed for MEDLINE]
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