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rdf:type |
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lifeskim:mentions |
umls-concept:C0205160,
umls-concept:C0244988,
umls-concept:C0542341,
umls-concept:C1332359,
umls-concept:C1334043,
umls-concept:C1514562,
umls-concept:C1704675,
umls-concept:C1704735,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221
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pubmed:issue |
38
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pubmed:dateCreated |
2006-9-19
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pubmed:abstractText |
Although prominent FRAT/GBP exhibits a limited degree of homology to Axin, the binding sites on GSK3 for FRAT/GBP and Axin may overlap to prevent the effect of FRAT/GBP in stabilizing beta-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3beta interaction protein (GSKIP), which binds to GSK3beta. We have defined a 25-amino acid region in the C-terminus of GSKIP that is highly similar to the GSK3beta interaction domain (GID) of Axin. Using an in vitro kinase assay, our results indicate that GSKIP is a good GSK3beta substrate, and both the full-length protein and a C-terminal fragment of GSKIP can block phosphorylation of primed and nonprimed substrates in different fashions. Similar to Axin GID(381-405) and FRATtide, synthesized GSKIPtide is also shown to compete with and/or block the phosphorylation of Axin and beta-catenin by GSK3beta. Furthermore, our data indicate that overexpression of GSKIP induces beta-catenin accumulation in the cytoplasm and nucleus as visualized by immunofluorescence. A functional assay also demonstrates that GSKIP-transfected cells have a significant effect on the transactivity of Tcf-4. Collectively, we define GSKIP as a naturally occurring protein that is homologous with the GSK3beta interaction domain of Axin and is able to negatively regulate GSK3beta of the Wnt signaling pathway.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
Sep
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pubmed:issn |
0006-2960
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pubmed:author |
pubmed-author:ChengTai-ShanTS,
pubmed-author:ChouChen-KungCK,
pubmed-author:ChouHe-YenHY,
pubmed-author:HongYi-RenYR,
pubmed-author:HowngShen-LongSL,
pubmed-author:HsiaoYun-LingYL,
pubmed-author:HsuChing-MeiCM,
pubmed-author:HuangChi-YingCY,
pubmed-author:HwangShiuh-LinSL,
pubmed-author:LeeChu-ICI,
pubmed-author:LieuAnn-ShungAS,
pubmed-author:LinChing-ChihCC,
pubmed-author:LohJoon-KhimJK,
pubmed-author:LuPei-JungPJ,
pubmed-author:WangChihueiC
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pubmed:issnType |
Print
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pubmed:day |
26
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pubmed:volume |
45
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
11379-89
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:16981698-Amino Acid Sequence,
pubmed-meshheading:16981698-Axin Protein,
pubmed-meshheading:16981698-Cells, Cultured,
pubmed-meshheading:16981698-Cloning, Molecular,
pubmed-meshheading:16981698-Glycogen Synthase Kinase 3,
pubmed-meshheading:16981698-HeLa Cells,
pubmed-meshheading:16981698-Humans,
pubmed-meshheading:16981698-Molecular Sequence Data,
pubmed-meshheading:16981698-Phosphorylation,
pubmed-meshheading:16981698-Protein Binding,
pubmed-meshheading:16981698-Protein Structure, Tertiary,
pubmed-meshheading:16981698-Protein Transport,
pubmed-meshheading:16981698-Repressor Proteins,
pubmed-meshheading:16981698-Sequence Alignment,
pubmed-meshheading:16981698-Sequence Homology,
pubmed-meshheading:16981698-Signal Transduction,
pubmed-meshheading:16981698-Wnt Proteins
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pubmed:year |
2006
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pubmed:articleTitle |
GSKIP is homologous to the Axin GSK3beta interaction domain and functions as a negative regulator of GSK3beta.
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pubmed:affiliation |
Graduate Institute of Biochemistry, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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