Linked Life Data

16543246

Source:http://linkedlifedata.com/resource/pubmed/id/16543246

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2006-5-8
pubmed:databankReference
pubmed:abstractText
Wnt signaling plays critical biological roles during normal embryonic development and homeostasis in adults. In the canonical pathway, binding of Wnt ligands to the Frizzled (Fzd) receptor and the low density lipoprotein-related receptor (LRP) 5 or LRP6 coreceptor initiates downstream signaling events leading to gene activation by beta-catenin and the T-cell factor (TCF)-lymphoid enhancer factor (LEF) family transcription factor complex. In this study, we provide several lines of evidence that the mouse Cristin/R-spondin family proteins function as Fzd8 and LRP6 receptor ligands and induce the canonical Wnt/beta-catenin signaling pathway, leading to TCF-dependent gene activation. First, conditioned medium containing Cristin/R-spondin proteins effectively induced reporter activity in a TCF-binding site-dependent manner. Second, stimulation of cells with Cristin/R-spondin was accompanied by stabilization of endogenous beta-catenin proteins and induction of canonical Wnt target genes. Third, Cristin/R-spondin proteins physically interacted with the extracellular domains of the LRP6 and Fzd8 receptors in vivo and in vitro. Interestingly, unlike canonical Wnt ligands, Cristin/R-spondin failed to form a ternary complex with both LRP6 and Fzd8 receptors, suggesting that R-spondin may activate the canonical Wnt signaling pathway by different mechanisms. Furthermore, Cristin/R-spondin proteins possess an intriguing positive modulatory activity on Wnt ligands, possibly through a direct interaction. Our findings expand the repertoire of ligands that induce beta-catenin/TCF-dependent gene activation and implicate the presence of active beta-catenin-dependent gene activation in a Wnt-free biological context.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
281
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
13247-57
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:16543246-Amino Acid Sequence, pubmed-meshheading:16543246-Animals, pubmed-meshheading:16543246-Cell Line, pubmed-meshheading:16543246-Gene Expression Regulation, Developmental, pubmed-meshheading:16543246-Heparin, pubmed-meshheading:16543246-Humans, pubmed-meshheading:16543246-Low Density Lipoprotein Receptor-Related Protein-6, pubmed-meshheading:16543246-Mice, pubmed-meshheading:16543246-Molecular Sequence Data, pubmed-meshheading:16543246-Multigene Family, pubmed-meshheading:16543246-Phylogeny, pubmed-meshheading:16543246-Protein Binding, pubmed-meshheading:16543246-Receptors, G-Protein-Coupled, pubmed-meshheading:16543246-Receptors, LDL, pubmed-meshheading:16543246-Signal Transduction, pubmed-meshheading:16543246-Thrombospondins, pubmed-meshheading:16543246-Transcriptional Activation, pubmed-meshheading:16543246-Wnt Proteins, pubmed-meshheading:16543246-beta Catenin
pubmed:year
2006
pubmed:articleTitle
Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression.
pubmed:affiliation
Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine 04074, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural