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Wnt Induces LRP6 Signalosomes and Promotes Dishevelled-Dependent LRP6 Phosphorylation
Josipa Bili,1Ya-Lin Huang,1Gary Davidson,1Timo Zimmermann,2Cristina-Maria Cruciat,1Mariann Bienz,3Christof Niehrs1*
Multiple signaling pathways, including Wnt signaling, participatein animal development, stem cell biology, and human cancer.Although many components of the Wnt pathway have been identified,unresolved questions remain as to the mechanism by which Wntbinding to its receptors Frizzled and Low-density lipoproteinreceptor–related protein 6 (LRP6) triggers downstreamsignaling events. With live imaging of vertebrate cells, weshow that Wnt treatment quickly induces plasma membrane–associatedLRP6 aggregates. LRP6 aggregates are phosphorylated and canbe detergent-solubilized as ribosome-sized multiprotein complexes.Phospho-LRP6 aggregates contain Wnt-pathway components but nocommon vesicular traffic markers except caveolin. The scaffoldprotein Dishevelled (Dvl) is required for LRP6 phosphorylationand aggregation. We propose that Wnts induce coclustering ofreceptors and Dvl in LRP6-signalosomes, which in turn triggersLRP6 phosphorylation to promote Axin recruitment and ß-cateninstabilization.
Caprin-2 enhances canonical Wnt signaling through regulating LRP5/6 phosphorylation.
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|Abstract »|Full Text »|PDF »
Wnt3a-Mediated Formation of Phosphatidylinositol 4,5-Bisphosphate Regulates LRP6 Phosphorylation.
W. Pan, S.-C. Choi, H. Wang, Y. Qin, L. Volpicelli-Daley, L. Swan, L. Lucast, C. Khoo, X. Zhang, L. Li, et al. (2008)
Science
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|Abstract »|Full Text »|PDF »
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Genes & Dev.
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|Abstract »|Full Text »|PDF »
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C. S. Cselenyi, K. K. Jernigan, E. Tahinci, C. A. Thorne, L. A. Lee, and E. Lee (2008)
PNAS
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|Abstract »|Full Text »|PDF »
Wnt Signal Amplification via Activity, Cooperativity, and Regulation of Multiple Intracellular PPPSP Motifs in the Wnt Co-receptor LRP6.
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283, 16115-16123
|Abstract »|Full Text »|PDF »
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121, 1793-1802
|Abstract »|Full Text »|PDF »
Initiation of Wnt signaling: control of Wnt coreceptor Lrp6 phosphorylation/activation via frizzled, dishevelled and axin functions.
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Development
135, 367-375
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2007: Signaling Breakthroughs of the Year.
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Science Signaling
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