Disruption of transforming growth factor-beta signaling in ELF beta-spectrin-deficient mice.
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.
Tang
Yi
Y
Laboratory of Developmental Biology, Department of Medicine, Georgetown University, Washington, DC 20007, USA.
Katuri
Varalakshmi
V
Dillner
Allan
A
Mishra
Bibhuti
B
Deng
Chu-Xia
CX
Mishra
Lopa
L
D000015:Abnormalities, Multiple; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D003285:Contractile Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005314:Embryonic and Fetal Development; D064448:Filamins; D018390:Gene Targeting; D016762:Genes, fos; D008099:Liver / Q000002:abnormalities / Q000196:embryology / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D010641:Phenotype; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D015398:Signal Transduction; D051899:Smad2 Protein; D051900:Smad3 Protein; D051901:Smad4 Protein; D013049:Spectrin / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism; D015533:Transcriptional Activation; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D003285:Contractile Proteins; D004268:DNA-Binding Proteins; D064448:Filamins; D008840:Microfilament Proteins; D010982:Platelet-Derived Growth Factor; D051899:Smad2 Protein; C497783:Smad2 protein, mouse; D051900:Smad3 Protein; C497791:Smad3 protein, mouse; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D013049:Spectrin