Wnt4 inhibits β‐catenin/TCF signalling by redirecting β‐catenin to the cell membrane

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Abstract
Background information . During embryonic development, β‐catenin is central both to the transcriptional activation of Wnt [wingless‐type MMTV (murine‐mammary‐tumour virus) integration site family] target genes and as a mediator of cell—cell adhesion. Signals that regulate its levels and subcellular localization are critical. One mechanism of Wnt signalling results in stabilization of β‐catenin protein, which leads to its translocation into the nucleus, where it interacts with TCF (T‐cell factor, HMG box) and activates transcription of target genes. Less well understood are mechanisms of Wnt signalling that do not involve β‐catenin stabilization and result in inhibition of β‐catenin‐mediated transcription. Results . Here, we show that a member of the Wnt protein family, Wnt4 (Wnt, member 4), regulates the subcellular localization of β‐catenin, redirecting it to the cell membrane. Unique among Wnts, this action does not affect the stability of β‐catenin but does prohibit its involvement in TCF gene transactivation. Conclusions . This novel mechanism suggests that Wnt4 acts as a switch between the two modes of β‐catenin function, transcriptional activation and cell—cell adhesion.