Research ArticleCell Biology

Bruton’s Tyrosine Kinase Revealed as a Negative Regulator of Wnt–β-Catenin Signaling

Sci. Signal.  26 May 2009:
Vol. 2, Issue 72, pp. ra25
DOI: 10.1126/scisignal.2000230

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BTK Checks Wnt–β-Catenin–Mediated Gene Expression

Dysregulated Wnt signaling is associated with several human diseases. James et al. now connect the Wnt–β-catenin pathway to Bruton’s tyrosine kinase, which is encoded by the gene responsible for X-linked agammaglobulinemia, a disease associated with decreased ability to fight infection due to a deficiency in B cells. By combining a small-molecule screen with a targeted siRNA screen, BTK was identified as an inhibitor of β-catenin–mediated gene expression. BTK did not alter the abundance of β-catenin in the presence or absence of Wnt; instead, it appeared to influence the stability of CDC73, a constituent of the PAF elongation complex and known binding partner of β-catenin. In B cells, CDC73 also inhibited β-catenin–mediated gene expression and BTK may act through this nuclear protein to restrain β-catenin’s transcriptional activity.