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Cell autonomous regulation of multiple Dishevelled-dependent pathways by mammalian Nkd

By Dong Yan, John B. Wallingford, Tian-Qiang Sun, April M. Nelson, Chie Sakanaka, Christoph Reinhard, Richard M. Harland, Wendy J. Fantl and Lewis T. Williams

Abstract

Genetic studies have identified Drosophila Naked Cuticle (Nkd) as an antagonist of the canonical Wnt/β-catenin signaling pathway, but its mechanism of action remains obscure [Zeng, W., Wharton, K. A., Jr., Mack, J. A., Wang, K., Gadbaw, M., et al. (2000) Nature (London) 403, 789–795]. Here we have cloned a cDNA encoding a mammalian homolog of Drosophila Nkd, mNkd, and demonstrated that mNkd interacts directly with Dishevelled. Dishevelled is an intracellular mediator of both the canonical Wnt pathway and planar cell polarity (PCP) pathway. Activation of the c-Jun-N-terminal kinase has been implicated in the PCP pathway. We showed that mNkd acts in a cell-autonomous manner not only to inhibit the canonical Wnt pathway but also to stimulate c-Jun-N-terminal kinase activity. Expression of mNkd disrupted convergent extension in Xenopus, consistent with a role for mNkd in the PCP pathway. These data suggest that mNkd may act as a switch to direct Dishevelled activity toward the PCP pathway, and away from the canonical Wnt pathway

Topics: Biological Sciences
Publisher: The National Academy of Sciences
Year: 2001
DOI identifier: 10.1073/pnas.071041898
OAI identifier: oai:pubmedcentral.nih.gov:31133
Provided by: PubMed Central
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