Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3–independent β-catenin degradation
By L. Topol, Xueyuan Jiang, Hosoon Choi, L. Garrett-Beal, Peter J. Carolan, Yingzi Yang. Journal of Cell Biology, 2003
742 citations recorded by the source corpus.
Wnts are secreted signaling molecules that can transduce their signals through several different pathways. Wnt-5a is considered a noncanonical Wnt as it does not signal by stabilizing β-catenin in many biological systems. We have uncovered a new noncanonical pathway through which Wnt-5a antagonizes the canonical Wnt pathway by promoting the degradation of β-catenin. This pathway is Siah2 and APC dependent, but GSK-3 and β-TrCP independent. Furthermore, we provide evidence that Wnt-5a also acts in vivo to promote β-catenin degradation in regulating mammalian limb development and possibly in suppressing tumor formation.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/eaf8f3155ab12e0fc34ccaa2e2d060545b38106f
How researchers see this paper
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In Molecular Biology
- G. Schulte
- J. Petersen
- J. Dijksterhuis
- R. Nusse
- Amanda J Mikels
- W. Birchmeier
- Hans Clevers
- T. Komori
Citations in the corpus
- Purified Wnt5a Protein Activates or Inhibits β-Catenin–TCF Signaling Depending on Receptor Context (2006, background): “have shown that Wnt5a-induced Ca2þ flux blocks canonical signaling downstream of b-catenin stabilization by inhibiting TCF-mediated transcription in a PTX-sensitive manner [16–18].”
- Multiple roles of mesenchymal β-catenin during murine limb patterning (2006, background): “It is interesting to note that Wnt5a, which is expressed in the distal limb mesenchyme, has recently been shown to downregulate - catenin levels (Topol et al., 2003).”
- Interactions between Sox9 and β-catenin control chondrocyte differentiation (2004, background): “A recent study showed that Wnt5a inhibits the canonical Wnt pathway by promoting -catenin degradation and that canonical Wnt activity in Wnt5a-null mutant limb buds is up-regulated (Topol et al. 2003).”
- INTERNATIONAL UNION OF BASIC AND CLINICAL PHARMACOLOGY REVIEW WNT/Frizzled signalling: receptor-ligand selectivity with focus on FZD-G protein signalling and its physiological relevance: IUPHAR Review 3 (2014, positive): “Moreover, different WNT signalling branches crosstalk as exemplified by the inhibition of WNT-3Ainduced signalling by WNT-5A (Topol et al., 2003; Mikels and Nusse, 2006).”