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Phosphorylation of ß-Catenin at S33, S37, or T41 Can Occur in the Absence of Phosphorylation at T45 in Colon Cancer Cells¹

The Sidney Kimmel Comprehensive Cancer Center [Z. W., B. V., K. W. K.] and The Howard Hughes Medical Institute [B. V.], The Johns Hopkins University Medical Institutions, Baltimore, Maryland 21231

Several previous studies in a variety of systems have suggested that phosphorylation at S45 of ß-catenin is essential for subsequent phosphorylation at more NH₂-terminal residues. Using genetic models expressing ß-catenin under endogenous regulation, we find that phosphorylation of ß-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.

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