RETRACTED: Regulation of β-catenin structure and activity by tyrosine phosphorylation (Retracted Article)

beta -Catenin plays a dual role as a key effector in the regulation of adherens junctions and as a transcriptional coactivator. Phosphorylation of Tyr-654, a residue placed in the last armadillo repeat of beta -catenin, decreases its binding to E-cadherin. We show here that phosphorylation of Tyr-654 also stimulates the association of beta -catenin to the basal transcription factor TATA-binding protein. The structural bases of these different affinities were investigated. Our results indicate that the beta -catenin C-terminal tail interacts with the armadillo repeat domain, hindering the association of the armadillo region to the TATA-binding protein or to E-cadherin. Phosphorylation of beta -catenin Tyr-654 decreases armadillo-C-terminal tail association, uncovering the last armadillo repeats. in a C-terminal-depleted beta -catenin, the presence of a negative charge at Tyr-654 does not affect the interaction of the TATA-binding protein to the armadillo domain. However, in the case of E-cadherin, the establishment of ion pairs dominates its association with beta -catenin, and its binding is greatly dependent on the absence of a negative charge at Tyr-654. Thus, phosphorylation of Tyr-654 blocks the E-cadherin-beta -catenin interaction, even though the steric hindrance of the C-tail is no longer present. These results explain how phosphorylation of beta -catenin in Tyr-654 modifies the tertiary structure of this protein and the interaction with its different partners.