PR130 is a modulator of the Wnt-signaling cascade that counters repression of the antagonist Naked cuticle

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 Writ antagonist that itself is induced by Writ signaling to keep Writ 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 Writ 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 Writ-signaling pathway, both in cell culture and during development. We find that PR130 modulates Writ signal transduction by restricting the ability of Naked cuticle to function as a Writ inhibitor. Our data establish PR130 as a modulator of the Wnt-signaling pathway and suggest a mechanism of Writ 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.