| Title: | The Axin-like protein PRY-1 is a negative regulator of a canonical Wnt pathway in C. elegans |
| Author(s): | Korswagen HC; Coudreuse DY; Betist MC; van de Water S; Zivkovic D; Clevers HC; |
| Address: | "Hubrecht Laboratory, Netherlands Institute for Developmental Biology, 3584 CT Utrecht, The Netherlands. rkors@niob.knaw.nl" |
| ISSN/ISBN: | 0890-9369 (Print) 1549-5477 (Electronic) 0890-9369 (Linking) |
| Abstract: | "Axin, APC, and the kinase GSK3 beta are part of a destruction complex that regulates the stability of the Wnt pathway effector beta-catenin. In C. elegans, several Wnt-controlled developmental processes have been described, but an Axin ortholog has not been found in the genome sequence and SGG-1/GSK3 beta, and the APC-related protein APR-1 have been shown to act in a positive, rather than negative fashion in Wnt signaling. We have shown previously that the EGL-20/Wnt-dependent expression of the homeobox gene mab-5 in the Q neuroblast lineage requires BAR-1/beta-catenin and POP-1/Tcf. Here, we have investigated how BAR-1 is regulated by the EGL-20 pathway. First, we have characterized a negative regulator of the EGL-20 pathway, pry-1. We show that pry-1 encodes an RGS and DIX domain-containing protein that is distantly related to Axin/Conductin. Our results demonstrate that despite its sequence divergence, PRY-1 is a functional Axin homolog. We show that PRY-1 interacts with BAR-1, SGG-1, and APR-1 and that overexpression of PRY-1 inhibits mab-5 expression. Furthermore, pry-1 rescues the zebrafish axin1 mutation masterblind, showing that it can functionally interact with vertebrate destruction complex components. Finally, we show that SGG-1, in addition to its positive regulatory role in early embryonic Wnt signaling, may function as a negative regulator of the EGL-20 pathway. We conclude that a highly divergent destruction complex consisting of PRY-1, SGG-1, and APR-1 regulates BAR-1/beta-catenin signaling in C. elegans" |
| Keywords: | Adenomatous Polyposis Coli Protein/metabolism Amino Acid Sequence Animals Axin Protein Caenorhabditis elegans/*genetics/growth & development/*metabolism *Caenorhabditis elegans Proteins Calcium-Calmodulin-Dependent Protein Kinases/metabolism Carrier Prote; |
| Notes: | "MedlineKorswagen, Hendrik C Coudreuse, Damien Y M Betist, Marco C van de Water, Sandra Zivkovic, Danica Clevers, Hans C eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. 2002/05/23 Genes Dev. 2002 May 15; 16(10):1291-302. doi: 10.1101/gad.981802" |
