Background: The ancient and highly evolutionarily conserved Wnt signaling pathway is
critical in nearly all tissues and organs for an organism to develop normally from embryo through adult.
Wnt signaling is generally parsed into “canonical” or Wnt-β-catenin-dependent or “non-canonical”
β-catenin-independent signaling. Even though designating Wnt signaling as either canonical or noncanonical
allows for easier conceptual discourse about this signaling pathway, in fact canonical and
non-canonical Wnt crosstalk regulates complex nonlinear networks.
Objective: In this perspective, we discuss the integration of canonical and non-canonical Wnt signaling
via differential Kat3 (CBP and p300) coactivator usage, thereby regulating and coordinating gene expression
programs associated with both proliferation and cellular differentiation and morphogenesis.
Methods: Pharmacologic inhibitors, cell culture, real-time PCR, chromatin immunoprecipitation, protein
immunoprecipitation, Western blotting, reporter-luciferase, protein purification, site-directed
mutagenesis, in vitro phosphorylation and binding assays, and immunofluorescence were utilized.
Conclusion: Coordinated integration between both canonical and non-canonical Wnt pathways appears
to be crucial not only in the control of fundamental morphologic processes but also in the regulation of
normal as well as pathologic events. Such integration between both canonical and non-canonical Wnt
signaling is presumably effected via reversible phosphorylation mechanism (e.g., protein kinase C) to
regulate differential β-catenin/Kat3 coactivator usage in order to coordinate proliferation with
differentiation and adhesion.