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- Title
Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice.
- Authors
Tang, Yi; Katuri, Varalakshmi; Dillner, Allan; Mishra, Bibhuti; Deng, Chu-Xia; Mishra, Lopa
- 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.
- Publication
Science (New York, N.Y.), 2003, Vol 299, Issue 5606, p574
- ISSN
1095-9203
- Publication type
Journal Article
- DOI
10.1126/science.1075994