PROTEIN STRUCTURE AND FOLDING
Regulation of β-Catenin Structure and Activity by Tyrosine Phosphorylation*

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β-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 β-catenin, decreases its binding to E-cadherin. We show here that phosphorylation of Tyr-654 also stimulates the association of β-catenin to the basal transcription factor TATA-binding protein. The structural bases of these different affinities were investigated. Our results indicate that the β-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 β-catenin Tyr-654 decreases armadillo-C-terminal tail association, uncovering the last armadillo repeats. In a C-terminal-depleted β-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 β-catenin, and its binding is greatly dependent on the absence of a negative charge at Tyr-654. Thus, phosphorylation of Tyr-654 blocks the Ecadherin-β-catenin interaction, even though the steric hindrance of the C-tail is no longer present. These results explain how phosphorylation of β-catenin in Tyr-654 modifies the tertiary structure of this protein and the interaction with its different partners.

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Published, JBC Papers in Press, March 13, 2001, DOI 10.1074/jbc.M100194200

*

This work was supported by La Marató de TV3 Grant 983110 (to A. G. H.), Ministerio de Ciencia y Tecnologı́a Grant PM99-0064 (to M. D.), FEDER-Fondo Nacional I+D Fund Grants 2FD97-1491-C02-01 and 2FD97-1491-C02-02 (to A. G. H. and M. D., respectively), and Direcció General de Recerca Grants 1999SGR00245 and 1999SGR00102.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Recipients of predoctoral fellowships awarded by Ministerio de Educación y Ciencia and CIRIT (Generalitat de Catalunya), respectively.