rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2004-8-25
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pubmed:databankReference |
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pubmed:abstractText |
The transcriptional coactivator beta-catenin mediates Wnt growth factor signaling. In the absence of a Wnt signal, casein kinase 1 (CK1) and glycogen synthase kinase-3beta (GSK-3beta) phosphorylate cytosolic beta-catenin, thereby flagging it for recognition and destruction by the ubiquitin/proteosome machinery. Phosphorylation occurs in a multiprotein complex that includes the kinases, beta-catenin, axin, and the Adenomatous Polyposis Coli (APC) protein. The role of APC in this process is poorly understood. CK1epsilon and GSK-3beta phosphorylate APC, which increases its affinity for beta-catenin. Crystal structures of phosphorylated and nonphosphorylated APC bound to beta-catenin reveal a phosphorylation-dependent binding motif generated by mutual priming of CK1 and GSK-3beta substrate sequences. Axin is shown to act as a scaffold for substrate phosphorylation by these kinases. Phosphorylated APC and axin bind to the same surface of, and compete directly for, beta-catenin. The structural and biochemical data suggest a novel model for how APC functions in 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/Adenomatous Polyposis Coli Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Axin Protein,
http://linkedlifedata.com/resource/pubmed/chemical/CTNNB1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Casein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Catnb protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cytoskeletal Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Glycogen Synthase Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Trans-Activators,
http://linkedlifedata.com/resource/pubmed/chemical/Wnt Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/beta Catenin,
http://linkedlifedata.com/resource/pubmed/chemical/glycogen synthase kinase 3 beta
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
1097-2765
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pubmed:author |
|
pubmed:issnType |
Print
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pubmed:day |
27
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
511-21
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:15327768-Adenomatous Polyposis Coli Protein,
pubmed-meshheading:15327768-Amino Acid Sequence,
pubmed-meshheading:15327768-Animals,
pubmed-meshheading:15327768-Axin Protein,
pubmed-meshheading:15327768-Casein Kinases,
pubmed-meshheading:15327768-Crystallography, X-Ray,
pubmed-meshheading:15327768-Cytoskeletal Proteins,
pubmed-meshheading:15327768-Glycogen Synthase Kinase 3,
pubmed-meshheading:15327768-Humans,
pubmed-meshheading:15327768-Mice,
pubmed-meshheading:15327768-Models, Molecular,
pubmed-meshheading:15327768-Molecular Sequence Data,
pubmed-meshheading:15327768-Phosphorylation,
pubmed-meshheading:15327768-Protein Binding,
pubmed-meshheading:15327768-Protein Kinases,
pubmed-meshheading:15327768-Protein Structure, Tertiary,
pubmed-meshheading:15327768-Proto-Oncogene Proteins,
pubmed-meshheading:15327768-Repressor Proteins,
pubmed-meshheading:15327768-Signal Transduction,
pubmed-meshheading:15327768-Trans-Activators,
pubmed-meshheading:15327768-Wnt Proteins,
pubmed-meshheading:15327768-beta Catenin
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pubmed:year |
2004
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pubmed:articleTitle |
Mechanism of phosphorylation-dependent binding of APC to beta-catenin and its role in beta-catenin degradation.
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pubmed:affiliation |
Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94043, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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