beta -Catenin plays a dual role as a key effector in the regulation of adhe
rens junctions and as a transcriptional coactivator. Phosphorylation of Tyr
-654, a residue placed in the last armadillo repeat of beta -catenin, decre
ases its binding to E-cadherin. We show here that phosphorylation of Tyr-65
4 also stimulates the association of beta -catenin to the basal transcripti
on factor TATA-binding protein. The structural bases of these different aff
inities were investigated. Our results indicate that the beta -catenin C-te
rminal tail interacts with the armadillo repeat domain, hindering the assoc
iation of the armadillo region to the TATA-binding protein or to E-cadherin
. Phosphorylation of beta -catenin Tyr-654 decreases armadillo-C-terminal t
ail association, uncovering the last armadillo repeats. in a C-terminal-dep
leted 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 dominat
es its association with beta -catenin, and its binding is greatly dependent
on the absence of a negative charge at Tyr-654. Thus, phosphorylation of T
yr-654 blocks the E-cadherin-beta -catenin interaction, even though the ste
ric hindrance of the C-tail is no longer present. These results explain how
phosphorylation of beta -catenin in Tyr-654 modifies the tertiary structur
e of this protein and the interaction with its different partners.