A β-Catenin Identified by Functional Rather Than Sequence Criteria and Its Role in Wnt/MAPK Signaling

Wnt/MAPK signaling is a common variant of Wnt signaling in C. elegans and has been implicated in vertebrates. The sys-1 gene works with Wnt/MAPK signaling to control cell fates during C. elegans development. We report that the SYS-1 amino acid sequence is novel but that SYS-1 functions as beta-catenin: SYS-1 rescues a bar-1/beta-catenin null mutant, binds the POP-1/TCF beta-catenin binding domain, and coactivates POP-1-dependent transcription. Moreover, we provide genetic and molecular evidence that SYS-1 levels are crucial to POP-1 activity. Our results suggest that Wnt/MAPK signaling promotes POP-1 export from the nucleus to accommodate the limiting availability of its SYS-1/beta-catenin transcriptional coactivator. Discovery of SYS-1/beta-catenin extends our definition of beta-catenins and brings together aspects of the canonical mechanism for Wnt signaling with the noncanonical Wnt/MAPK mechanism. We discuss the idea that a similar pathway may be employed broadly in animal development.