Interaction of glycogen synthase kinase 3β with the DF3/MUC1 carcinoma-associated antigen and β-catenin

被引:220
作者
Li, YQ [1 ]
Bharti, A [1 ]
Chen, DS [1 ]
Gong, JL [1 ]
Kufe, D [1 ]
机构
[1] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
基金
新加坡国家研究基金会;
关键词
D O I
10.1128/MCB.18.12.7216
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The DF3/MUC1 mucin-like glycoprotein is highly overexpressed in human carcinomas. Recent studies have demonstrated that the cytoplasmic domain of MUC1 interacts with beta-catenin. Here we show that MUC1 associates with glycogen synthase kinase 3 beta (GSK3 beta). GSK3 beta binds directly to an STDRSPYE site in MUC1 and phosphorylates the serine adjacent to proline, Phosphorylation of MUC1 by GSK3 beta decreases binding of MUC1 to beta-catenin in vitro and in vivo. GSK3 beta-mediated phosphorlylation of MUC1 had no apparent effect on beta-catenin levels or the transcriptional coactivation function of beta-catenin, The results, however, demonstrate that MUC1 expression decreases binding of beta-catenin to the E-cadherin cell adhesion molecule. Negative regulation of the beta-catenin-MUC1 interaction by GSK3 beta is associated with restoration of the complex between beta-catenin and E-cadherin. These findings indicate that GSK3 beta decreases the interaction of MUC1 with beta-catenin and that overexpression of MUC1 in the absence of GSK3 beta activity inhibits formation of the E-cadherin-beta-catenin complex.
引用
收藏
页码:7216 / 7224
页数:9
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