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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
18
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pubmed:dateCreated |
2006-5-1
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pubmed:abstractText |
Wnt signaling acts in part through the low density lipoprotein receptor-related transmembrane proteins LRP5 and LRP6 to regulate embryonic development and stem cell proliferation. Up-regulated signaling is associated with many forms of cancer. Casein kinase I epsilon (CKIepsilon) is a known component of the Wnt-beta-catenin signaling pathway. We find that CKIepsilon binds to LRP5 and LRP6 in vitro and in vivo and identify three CKIepsilon-specific phosphorylation sites in LRP6. Two of the identified phosphorylation sites, Ser1420 and Ser1430, influence Wnt signaling in vivo, since LRP6 with mutation of these sites is a more potent activator of both beta-catenin accumulation and Lef-1 reporter activity. Whereas Wnt3a regulates CKIepsilon kinase activity, LRP6 does not, placing CKIepsilon upstream of LRP6. Mutation of LRP6 Ser1420 and Ser1430 to alanine strengthens its interaction with axin, suggesting a mechanism by which CKIepsilon may negatively regulate Wnt signaling. The role of CKIepsilon is therefore more complex than was previously appreciated. Generation of active CKIepsilon may induce a negative feedback loop by phosphorylation of sites on LRP5/6 that modulate axin binding and hence beta-catenin degradation.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinase Iepsilon,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/LRP5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/LRP6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphoid Enhancer-Binding Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/WNT3A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt3A Protein,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
281
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
12233-41
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16513652-Amino Acid Sequence,
pubmed-meshheading:16513652-Casein Kinase Iepsilon,
pubmed-meshheading:16513652-Humans,
pubmed-meshheading:16513652-LDL-Receptor Related Proteins,
pubmed-meshheading:16513652-Low Density Lipoprotein Receptor-Related Protein-5,
pubmed-meshheading:16513652-Low Density Lipoprotein Receptor-Related Protein-6,
pubmed-meshheading:16513652-Lymphoid Enhancer-Binding Factor 1,
pubmed-meshheading:16513652-Molecular Sequence Data,
pubmed-meshheading:16513652-Phosphorylation,
pubmed-meshheading:16513652-Sequence Homology, Amino Acid,
pubmed-meshheading:16513652-Signal Transduction,
pubmed-meshheading:16513652-Wnt Proteins,
pubmed-meshheading:16513652-Wnt3 Protein,
pubmed-meshheading:16513652-Wnt3A Protein,
pubmed-meshheading:16513652-beta Catenin
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pubmed:year |
2006
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pubmed:articleTitle |
Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation.
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pubmed:affiliation |
Department of Oncological Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112-5550, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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