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Open AccessArticle

Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B

Department of Cell Biology and Human Anatomy, School of Medicine, University of California, Davis, CA 95616, USA
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Author to whom correspondence should be addressed.
Genes 2018, 9(4), 196; https://doi.org/10.3390/genes9040196
Received: 19 February 2018 / Revised: 24 March 2018 / Accepted: 26 March 2018 / Published: 5 April 2018
(This article belongs to the Special Issue Wnt Signaling in Stem Cells)
Noncanonical WNT pathways function independently of the β-catenin transcriptional co-activator to regulate diverse morphogenetic and pathogenic processes. Recent studies showed that noncanonical WNTs, such as WNT5A, can signal the degradation of several downstream effectors, thereby modulating these effectors’ cellular activities. The protein domain(s) that mediates the WNT5A-dependent degradation response, however, has not been identified. By coupling protein mutagenesis experiments with a flow cytometry-based degradation reporter assay, we have defined a protein domain in the kinesin superfamily protein KIF26B that is essential for WNT5A-dependent degradation. We found that a human disease-causing KIF26B mutation located at a conserved amino acid within this domain compromises the ability of WNT5A to induce KIF26B degradation. Using pharmacological perturbation, we further uncovered a role of glycogen synthase kinase 3 (GSK3) in WNT5A regulation of KIF26B degradation. Lastly, based on the identification of the WNT5A-responsive domain, we developed a new reporter system that allows for efficient profiling of WNT5A-KIF26B signaling activity in both somatic and stem cells. In conclusion, our study identifies a new protein domain that mediates WNT5A-dependent degradation of KIF26B and provides a new tool for functional characterization of noncanonical WNT5A signaling in cells. View Full-Text
Keywords: WNT5A; KIF26B; ROR receptors; Frizzled receptors; Dishevelled; GSK3; protein degradation; mesenchymal stem cells WNT5A; KIF26B; ROR receptors; Frizzled receptors; Dishevelled; GSK3; protein degradation; mesenchymal stem cells
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Karuna, E.P.; Choi, S.S.; Scales, M.K.; Hum, J.; Cohen, M.; Fierro, F.A.; Ho, H.-Y.H. Identification of a WNT5A-Responsive Degradation Domain in the Kinesin Superfamily Protein KIF26B. Genes 2018, 9, 196.

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