原创力文档bili inhibits wntβ-catenin signaling by regulating the recruitment of axin to lrp6的招聘,并抑制wntβ-catenin信号通过调节轴蛋白lrp6.pdfVIP
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bili inhibits wntβ-catenin signaling by regulating the recruitment of axin to lrp6的招聘,并抑制wntβ-catenin信号通过调节轴蛋白lrp6
Bili Inhibits Wnt/b-Catenin Signaling by Regulating the
Recruitment of Axin to LRP6
1. 2. 1. 1 1
Lorna S. Kategaya , Binita Changkakoty , Travis Biechele , William H. Conrad , Ajamete Kaykas ,
2 1
Ramanuj DasGupta , Randall T. Moon *
1 Department of Pharmacology, Howard Hughes Medical Institute (HHMI), University of Washington School of Medicine and Institute for Stem Cell and Regenerative
Medicine, University of Washington School of Medicine, Seattle, Washington, United States of America, 2 Department of Pharmacology and Cancer Institute, New York
University School of Medicine, New York, New York, United States of America
Abstract
Background: Insights into how the Frizzled/LRP6 receptor complex receives, transduces and terminates Wnt signals will
enhance our understanding of the control of the Wnt/ß-catenin pathway.
Methodology/Principal Findings: In pursuit of such insights, we performed a genome-wide RNAi screen in Drosophila cells
expressing an activated form of LRP6 and a b-catenin-responsive reporter. This screen resulted in the identification of Bili, a
Band4.1-domain containing protein, as a negative regulator of Wnt/b-catenin signaling. We found that the expression of Bili
in Drosophila embryos and larval imaginal discs significantly overlaps with the expression of Wingless (Wg), the Drosophila
Wnt ortholog, which is consistent with a potential function for Bili in the Wg pathway. We then tested the functions of Bili in
both invertebrate and vertebrate animal model systems. Loss-of-function studies in Drosophila and zebrafish embryos, as
well as human cultured cells, demonstrate that Bili is an evolutionarily conserved antagonist of Wnt/
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