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Science 24 January 2003:
Vol. 299. no. 5606, pp. 574 - 577
DOI: 10.1126/science.1075994
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Reports

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

Yi Tang,1 Varalakshmi Katuri,1 Allan Dillner,1 Bibhuti Mishra,1* Chu-Xia Deng,2* Lopa Mishra134*

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.

1 Laboratory of Developmental Biology, Department of Medicine, Georgetown University, Washington, DC 20007, USA.
2 Genetics of Development and Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20878, USA.
3 Department of Veterans Affairs at Washington, DC 20422, USA.
4 Fels Institute for Cancer Research and Molecular Biology, Temple University, Philadelphia, PA 19140, USA.
*   To whom correspondence should be addressed. E-mail: lm229{at}georgetown.edu and lopamishra{at}yahoo.com

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