Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

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

RESEARCH ARTICLES

Editor's Summary

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.

Citation: R. G. James, T. L. Biechele, W. H. Conrad, N. D. Camp, D. M. Fass, M. B. Major, K. Sommer, X. Yi, B. S. Roberts, M. A. Cleary, W. T. Arthur, M. MacCoss, D. J. Rawlings, S. J. Haggarty, R. T. Moon, Bruton’s Tyrosine Kinase Revealed as a Negative Regulator of Wnt–β-Catenin Signaling. Sci. Signal. 2, ra25 (2009).

Read the Full Text

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Oncogenic MicroRNA-155 Down-regulates Tumor Suppressor CDC73 and Promotes Oral Squamous Cell Carcinoma Cell Proliferation: IMPLICATIONS FOR CANCER THERAPEUTICS.
M. I. Rather, M. N. Nagashri, S. S. Swamy, K. S. Gopinath, and A. Kumar (2013)
J. Biol. Chem. 288, 608-618
   Abstract »    Full Text »    PDF »
Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations.
B. K. Cornes, C. C. Khor, M. E. Nongpiur, L. Xu, W.-T. Tay, Y. Zheng, R. Lavanya, Y. Li, R. Wu, X. Sim, et al. (2012)
Hum. Mol. Genet. 21, 437-445
   Abstract »    Full Text »    PDF »
Identification of {beta}-catenin as a target of the intracellular tyrosine kinase PTK6.
H. L. Palka-Hamblin, J. J. Gierut, W. Bie, P. M. Brauer, Y. Zheng, J. M. Asara, and A. L. Tyner (2010)
J. Cell Sci. 123, 236-245
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882