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

被引：221

作者：

Tang, Y

Katuri, V

Dillner, A

Mishra, B ^{[1
]}

Deng, CX

Mishra, L

机构：

[1] NIDDKD, Genet Dev & Dis Branch, NIH, US Dept HHS, Bethesda, MD 20878 USA

[2] Georgetown Univ, Dept Med, Dev Biol Lab, Washington, DC 20007 USA

[3] Dept Vet Affairs, Washington, DC 20422 USA

[4] Temple Univ, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA

来源：

SCIENCE | 2003年 / 299卷 / 5606期

关键词：

D O I：

10.1126/science.1075994

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：574 / 577

页数：5

共 22 条

[1] Spectrin and ankyrin-based pathways: Metazoan inventions for integrating cells into tissues [J].