Nodal signaling uses activin and transforming growth factor-β receptor-regulated Smads

99Citations
Citations of this article
84Readers
Mendeley users who have this article in their library.

This article is free to access.

Abstract

Nodal, a member of the transforming growth factor (TGF-β) superfamily, is implicated in many events critical to the early vertebrate embryo, including mesoderm formation, anterior patterning, and left-right axis specification. Here we define the intracellular signaling pathway induced by recombinant nodal protein treatment of P19 embryonal carcinoma cells. Nodal signaling activates pAR3-Lux, a luciferase reporter previously shown to respond specifically to activin and TGF-β. However, nodal is unable to induce pTlx2-Lux, a reporter specifically responsive to bone morphogenetic proteins. We also demonstrate that nodal induces p(CAGA)12, a reporter previously shown to be specifically activated by Smad3. Expression of a dominant negative Smad2 significantly reduces the level of luciferase reporter activity induced by nodal treatment. Finally, we show that nodal signaling rapidly leads to the phosphorylation of Smad2. These results provide the first direct biochemical evidence that nodal signaling is mediated by both activin. TGF-β pathway Smads, Smad2 and Smad3. We also show here that the extracellular cripto protein is required for nodal signaling, making it distinct from activin or TGF-β signaling.

Cite

CITATION STYLE

APA

Kumar, A., Novoselov, V., Celeste, A. J., Wolfman, N. M., Ten Dijke, P., & Kuehn, M. R. (2001). Nodal signaling uses activin and transforming growth factor-β receptor-regulated Smads. Journal of Biological Chemistry, 276(1), 656–661. https://doi.org/10.1074/jbc.M004649200

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free