Phosphorylation of beta-catenin at S33, S37, or T41 can occur in the absence of phosphorylation at T45 in colon cancer cells.

Several previous studies in a variety of systems have suggested that phosphorylation at S45 of beta-catenin is essential for subsequent phosphorylation at more NH(2)-terminal residues. Using genetic models expressing beta-catenin under endogenous regulation, we find that phosphorylation of beta-catenin at S45 is not required for phosphorylation at residues S33, S37, or T41 in human colon cancer cells, in contrast to prevailing models. These findings suggest that there are important cell- and organism-specific differences in even the most highly conserved signaling pathways and emphasize the importance of examining these pathways in the cancer cell types in which the pathways are actually deregulated.