Tomoregulin-1 (TMEFF1) inhibits nodal signaling through direct binding to the nodal coreceptor Cripto

• DOI: 10.1101/gad.1127703
• Publication Date: 2003-10-21T00:22:48Z
• Authors: Paul W. Harms; Chenbei Chang
• Keywords: Nodal signaling; Activin receptor; Immunoprecipitation

Transforming growth factor β (TGF-β) signals regulate multiple processes during development and in adult. We recently showed that tomoregulin-1 (TMEFF1), a transmembrane protein, selectively inhibits nodal but not activin early Xenopus embryos. Here we report TMEFF1 binds to the coreceptor Cripto, does associate with either or type I ALK (activin receptor-like kinase) 4 receptor coimmunoprecipitation assays. The inhibition of signaling by ectodermal explants is rescued wild-type mutant forms Cripto. Furthermore, show Cripto-FRL1-Cryptic (CFC) domain which essential for its binding ALK4, also important interaction TMEFF1. Our results demonstrate first time can be regulated novel mechanism blocking Cripto coreceptor.