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    題名: GSKIP is homologous to the Axin GSK3 beta interaction domain and functions as a negative regulator of GSK3 beta
    作者: Chou, HY;Howng, SL;Cheng, TS;Hsiao, YL;Lieu, AS;Loh, JK;Hwang, SL;Lin, CC;Hsu, CM;Wang, C;Lee, CI;Lu, PJ;Chou, CK;Huang, CY;Hong, YR
    貢獻者: Division of Molecular and Genomic Medicine
    摘要: 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, GSK3 beta interaction protein (GSKIP), which binds to GSK3 beta. We have defined a 25-amino acid region in the C-terminus of GSKIP that is highly similar to the GSK3 beta interaction domain (GID) of Axin. Using an in vitro kinase assay, our results indicate that GSKIP is a good GSK3 beta 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 GSK3 beta. 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 GSK3 beta interaction domain of Axin and is able to negatively regulate GSK3 beta of the Wnt signaling pathway.
    關鍵詞: Biochemistry & Molecular Biology
    日期: 2006-09-26
    關聯: Biochemistry. 2006 Sep;45(38):11379-11389.
    Link to: http://dx.doi.org/10.1021/bi061147r
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-2960&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000240575900014
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=33749022255
    顯示於類別:[黃奇英(1998-2005)] 期刊論文

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