Evidence that Armadillo Transduces Wingless by Mediating Nuclear Export or Cytosolic Activation of Pangolin

Secreted proteins of the Wnt family have profound organizing roles during animal development and are transduced via the activities of the Frizzled (Fz) class of transmembrane receptors and the TCF/LEF/Pangolin class of transcription factors. β-catenins, including Drosophila Armadillo (Arm), link activation of Fz at the cell surface to transcriptional regulation by TCF in the nucleus. The consensus view is that Wnt signaling induces β-catenin to enter the nucleus and combine with TCF to form a transcription factor complex in which TCF binds DNA and the C-terminal domain of β-catenin activates transcription. Here, we present findings, which challenge this view and suggest instead that β-catenin may transduce Wnt signals by exporting TCF from the nucleus or activating it in the cytoplasm.