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PMID: 18083125 Published · ppublish English Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Multiple PPPS/TP motifs act in a combinatorial fashion to transduce Wnt signaling through LRP6.

FEBS letters ·Vol. 582 ·No. 2 ·2008-01-23 ·Pages 255-61

Wolf J, Palmby TR, Gavard J, Williams BO, Gutkind JS

Abstract

Binding of Wnt to Frizzled, and either of two members of the low-density-lipoprotein receptor-related protein family, LRP5/6, leads to beta-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 beta-catenin activation. Instead, we show that each LRP6 PPPS/TP motif contributes in a combinatorial fashion to activate the canonical Wnt-beta-catenin pathway.

MeSH Terms
Base Sequence Cell Line Conserved Sequence DNA Primers Fluorescent Antibody Technique Humans LDL-Receptor Related Proteins/chemistry,metabolism Low Density Lipoprotein Receptor-Related Protein-6 Reverse Transcriptase Polymerase Chain Reaction Signal Transduction Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
DNA Primers LDL-Receptor Related Proteins LRP6 protein, human Low Density Lipoprotein Receptor-Related Protein-6 Wnt Proteins beta Catenin
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Wolf Joshua
Oral and Pharyngeal Cancer Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, 30 Convent Drive, Bethesda, MD 20892, USA.
Palmby Todd R
Gavard Julie
Williams Bart O
Gutkind J Silvio
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Article Info
Journal
FEBS letters
Abbr.
FEBS Lett
ISSN
0014-5793
DOI
10.1016/j.febslet.2007.12.013
Published
2008-01-23
Epub
2007-00-18
Pages
255-61
Language
English
Region
England
NLM ID
0155157
PMCID
PMC2268019
Subset
IM
Grants
Intramural NIH HHS · Z01 DE000551-16 · United States
External Links
PubMed source DOI: 10.1016/j.febslet.2007.12.013 PMC Full Text View journal details
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