Pr130 is a Modulator of the Wnt-signaling Cascade That Counters Repression of the Antagonist Naked Cuticle.
From: Division of Molecular Carcinogenesis and Center for Biomedical Genetics, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Proceedings of the National Academy of Sciences of the United States of America
- Publish Date: Apr 2006
- ISSN: 0027-8424
- Volume: 103
- Issue: 14
- Pages: 5397-402
- Medium: Print
- Language: English
- Citation (JAMA): Creyghton Menno P, Roël Giulietta, Eichhorn Pieter J A, et al. Pr130 is a Modulator of the Wnt-signaling Cascade That Counters Repression of the Antagonist Naked Cuticle.. Proc. Natl. Acad. Sci. U.S.A. Apr 2006;103:5397-402
Abstract
The Wnt-signaling cascade is required for several crucial steps during early embryogenesis, and its activity is modulated by various agonists and antagonists to provide spatiotemporal-specific signaling. Naked cuticle is a Wnt antagonist that itself is induced by Wnt signaling to keep Wnt signaling in check. Little is known about the regulation of this antagonist. We have recently shown that the protein phosphatase 2A regulatory subunit PR72 is required for the inhibitory effect of Naked cuticle on Wnt signaling. In the present study, we show that PR130, which has an N terminus that differs from that of PR72 but shares the same C terminus, also interacts with Naked cuticle but instead functions as an activator of the Wnt-signaling pathway, both in cell culture and during development. We find that PR130 modulates Wnt signal transduction by restricting the ability of Naked cuticle to function as a Wnt inhibitor. Our data establish PR130 as a modulator of the Wnt-signaling pathway and suggest a mechanism of Wnt signal regulation in which the inhibitory activity of Naked cuticle is determined by the relative level of expression of two transcripts of the same protein phosphatase 2A regulatory subunit.
Mesh Headings (Keywords): Animals, Carrier Proteins, Cell Line, Humans, In Situ Hybridization, Phosphoprotein Phosphatases, Protein Phosphatase 2, Signal Transduction, Wnt Proteins, Xenopus
Check for Full Text / PubMed Unique Identifier (PMID): 16567647
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