Molecular Biology of the Cell Sign up for new MBC in Press e-TOCs!

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Originally published as MBC in Press, 10.1091/mbc.E08-02-0187 on April 9, 2008

Vol. 19, Issue 6, 2588-2596, June 2008

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
E08-02-0187v1
19/6/2588    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Google Scholar
Right arrow Articles by Kim, K.-A.
Right arrow Articles by Abo, A.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, K.-A.
Right arrow Articles by Abo, A.

R-Spondin Family Members Regulate the Wnt Pathway by a Common Mechanism

Kyung-Ah Kim, Marie Wagle, Karolyn Tran, Xiaoming Zhan, Melissa A. Dixon, Shouchun Liu, Delphine Gros, Wouter Korver, Shirlee Yonkovich, Nenad Tomasevic, Minke Binnerts, and Arie Abo

Research Department, Nuvelo, San Carlos, CA 94070

Submitted February 21, 2008; Revised March 24, 2008; Accepted April 2, 2008
Monitoring Editor: Marianne Bronner-Fraser

The R-Spondin (RSpo) family of secreted proteins is implicated in the activation of the Wnt signaling pathway. Despite the high structural homology between the four members, expression patterns and phenotypes in knockout mice have demonstrated striking differences. Here we dissected and compared the molecular and cellular function of all RSpo family members. Although all four RSpo proteins activate the canonical Wnt pathway, RSpo2 and 3 are more potent than RSpo1, whereas RSpo4 is relatively inactive. All RSpo members require Wnt ligands and LRP6 for activity and amplify signaling of Wnt3A, Wnt1, and Wnt7A, suggesting that RSpo proteins are general regulators of canonical Wnt signaling. Like RSpo1, RSpo2-4 antagonize DKK1 activity by interfering with DKK1 mediated LRP6 and Kremen association. Analysis of RSpo deletion mutants indicates that the cysteine-rich furin domains are sufficient and essential for the amplification of Wnt signaling and inhibition of DKK1, suggesting that Wnt amplification by RSpo proteins may be a direct consequence of DKK1 inhibition. Together, these findings indicate that RSpo proteins modulate the Wnt pathway by a common mechanism and suggest that coexpression with specific Wnt ligands and DKK1 may determine their biological specificity in vivo.

This was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E08-02-0187) on April 9, 2008.

Address correspondence to: Arie Abo (aabo{at}nuvelo.com).






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
Copyright © 2008 by The American Society for Cell Biology. Terms of copyright protection, warranties, and disclaimers.