| | Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6Edited by Richard Marais Received 8 October 2007; received in revised form 5 December 2007; accepted 6 December 2007. published online 14 December 2007. Abstract Binding of Wnt to Frizzled, and either of two members of the low-density-lipoprotein receptor-related protein family, LRP5/6, leads to β-catenin activation by a poorly understood mechanism. LRP5/6 exhibit five highly conserved PPPS/TP motifs in their intracellular region, among which the first PPPS/TP site is rapidly phosphorylated upon Wnt stimulation. By the use of full-length LRP6 mutants harboring multiple mutations involving the five PPPS/TP motifs, we found that this first PPPS/TP phosphoacceptor site is alone not sufficient or strictly necessary for β-catenin activation. Instead, we show that each LRP6 PPPS/TP motif contributes in a combinatorial fashion to activate the canonical Wnt-β-catenin pathway. a Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Building 30, Room 211, Bethesda, MD 20892, USA b Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, MI 49503-2518, USA  Corresponding author. Fax: +1 301 402 0823.
PII: S0014-5793(07)01272-0 doi:10.1016/j.febslet.2007.12.013 © 2007 Federation of European Biochemical Societies. Published by Elsevier BV. All rights reserved. | |
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ABSTRACT
