Schematic representation of the classic Wnt signaling pathway and model of US28-mediated activation of ß-catenin signaling pathway.

The left side of the model indicates components of the classic Wnt/Frizzled mediated activation of ß-catenin. In this pathway the disruption complex (Axin, APC) that enables GSK3ß- and Caseine kinase 1 (CK1)-mediated phosphorylation of ß-catenin leading to its degradation, is disrupted in a Dishevelled-mediated way upon Wnt binding to Frizzled/LRP. US28 activates ß-catenin signaling in a ligand-dependent and independent manner, involving respectively Gα_12/13 and Gα_q proteins and respective RhoGEFs, converging at RhoA/ROCK, resulting in increased Tcf-Lef transcriptional activation.