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

Richard G. James; Travis L. Biechele; William H. Conrad; Nathan D. Camp; Daniel M. Fass; Michael B. Major; Karen Sommer; XianHua Yi; Brian S. Roberts; Michele A. Cleary; William T. Arthur; Michael MacCoss; David J. Rawlings; Stephen J. Haggarty; Randall T. Moon

doi:10.1126/scisignal.2000230

Research ArticleCell Biology

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

Richard G. James¹,²,*,
Travis L. Biechele¹,²,*,
William H. Conrad¹,²,
Nathan D. Camp¹,²,
Daniel M. Fass³,†,
Michael B. Major¹,²,
Karen Sommer⁴,
XianHua Yi⁵,
Brian S. Roberts⁶,
Michele A. Cleary⁶,
William T. Arthur⁶,
Michael MacCoss⁵,
David J. Rawlings⁴,
Stephen J. Haggarty³,†, and
Randall T. Moon¹,²,‡

¹Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
²Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.
³The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Street, Cambridge, MA 02141, USA.
⁴Departments of Pediatrics and Immunology, Seattle Children’s Research Institute, 1900 Ninth Avenue, C9S-7, Seattle, WA 98101, USA.
⁵Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.
⁶Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co Inc., 401 Terry Avenue N, Seattle, WA 98109, USA.

↵‡To whom correspondence should be addressed. E-mail: rtmoon{at}u.washington.edu

↵* These authors contributed equally to this work.
↵† Present address: Center for Human Genetic Research, Massachusetts General Hospital, 185 Cambridge Street, Boston, MA 02114, USA.

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

Richard G. James

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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Travis L. Biechele

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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William H. Conrad

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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Nathan D. Camp

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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Daniel M. Fass

3The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Street, Cambridge, MA 02141, USA.

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Michael B. Major

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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Karen Sommer

4Departments of Pediatrics and Immunology, Seattle Children’s Research Institute, 1900 Ninth Avenue, C9S-7, Seattle, WA 98101, USA.

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XianHua Yi

5Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

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Brian S. Roberts

6Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co Inc., 401 Terry Avenue N, Seattle, WA 98109, USA.

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Michele A. Cleary

6Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co Inc., 401 Terry Avenue N, Seattle, WA 98109, USA.

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William T. Arthur

6Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck & Co Inc., 401 Terry Avenue N, Seattle, WA 98109, USA.

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Michael MacCoss

5Department of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98195, USA.

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David J. Rawlings

4Departments of Pediatrics and Immunology, Seattle Children’s Research Institute, 1900 Ninth Avenue, C9S-7, Seattle, WA 98101, USA.

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Stephen J. Haggarty

3The Broad Institute of Harvard University and Massachusetts Institute of Technology, 7 Cambridge Street, Cambridge, MA 02141, USA.

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Randall T. Moon

1Department of Pharmacology, Howard Hughes Medical Institute, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

2Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Box 357370, Seattle, WA 98195, USA.

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For correspondence: rtmoon@u.washington.edu

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

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