TY - JOUR
T1 - Disruption of transforming growth factor-β signaling in ELF β-spectrin-deficient mice
AU - Tang, Yi
AU - Katuri, Varalakshmi
AU - Dillner, Allan
AU - Mishra, Bibhuti
AU - Deng, Chu Xia
AU - Mishra, Lopa
PY - 2003/1/24
Y1 - 2003/1/24
N2 - Disruption of the adaptor protein ELF, a β-spectrin, leads to disruption of transforming growth factor-β (TGF-β) 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-β 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-β-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.
AB - Disruption of the adaptor protein ELF, a β-spectrin, leads to disruption of transforming growth factor-β (TGF-β) 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-β 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-β-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.
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U2 - 10.1126/science.1075994
DO - 10.1126/science.1075994
M3 - Article
C2 - 12543979
AN - SCOPUS:0037462502
SN - 0036-8075
VL - 299
SP - 574
EP - 577
JO - Science
JF - Science
IS - 5606
ER -