A beta-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.
Kidd
Ambrose R
AR
Program in Cellular and Molecular Biology, University of Wisconsin-Madison, Wisconsin 53706, USA.
Miskowski
Jennifer A
JA
Siegfried
Kellee R
KR
Sawa
Hitoshi
H
Kimble
Judith
J
D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D006609:High Mobility Group Proteins / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051153:Wnt Proteins
D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D006609:High Mobility Group Proteins; D036341:Intercellular Signaling Peptides and Proteins; C502083:Sys-1 protein, C elegans; D015534:Trans-Activators; D014157:Transcription Factors; D051153:Wnt Proteins; C096787:pop-1 protein, C elegans; D020928:Mitogen-Activated Protein Kinases