Assembly of Dishevelled 3-based supermolecular complexes via phosphorylation and Axin.
| Autor: | Yokoyama N; Departments of Pharmacology, School of Medicine, State University of New York at Stony Brook, Stony Brook, NY, 11794-8651, USA. noriko@pharm.stonybrook.edu., Markova NG, Wang HY, Malbon CC |
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| Jazyk: | angličtina |
| Zdroj: | Journal of molecular signaling [J Mol Signal] 2012 Jun 29; Vol. 7 (1), pp. 8. Date of Electronic Publication: 2012 Jun 29. |
| DOI: | 10.1186/1750-2187-7-8 |
| Abstrakt: | Background: Dishevelled-3 (Dvl3) is a multivalent scaffold essential to cell signaling in development. Dsh/Dvls enable a myriad of protein-protein interactions in Wnt signaling. In the canonical Wnt/β-catenin pathway specifically, Dvl3 polymerizes to form dynamic protein aggregates, so-called "signalsomes", which propagate signals from the Wnt receptor Frizzled to downstream elements. Results: Very large Dvl3-based supermolecular complexes form in response to Wnt3a. These complexes are identified by steric-exclusion chromatography, affinity pull-downs, proteomics, and fluorescence correlation microscopy (fcs). In the current work, the roles of Dvl3 phosphorylation and of Axin in the assembly of Dvl3-based supermolecular complexes in response to Wnt3a are probed in totipotent mouse F9 teratocarcinoma cells. Point mutations of phosphorylation sites of Dvl3 which interfere with Lef/Tcf-sensitive transcriptional activation by Wnt3a are shown to interfere more proximally with the assembly of Dvl3-based supermolecular complexes. Axin, a Dvl-interacting protein, plays a central role in organizing the beta-catenin destruction complex. The assembly of Dvl3-based supermolecular complexes is blocked either by depletion of Axin or by mutation of Axin sites necessary for polymerization in response to Wnt3a. Conclusion: These data demonstrate that Wnt3a activation of the canonical pathway requires specific phosphorylation events as well as Axin to assemble very large, Dvl3-based supermolecular complexes; these complexes are a prerequisite to activation of Lef/Tcf-sensitive transcription. |
| Databáze: | MEDLINE |
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