GSKIP Is Homologous to the Axin GSK3 Interaction Domain and Functions as a Negative Regulator of GSK3
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- 作者：He-Yen Chou ; Shen-Long Howng ; Tai-Shan Cheng ; Yun-Ling Hsiao ; Ann-Shung Lieu ; Joon-Khim Loh ; Shiuh-Lin Hwang ; Ching-Chih Lin ; Ching-Mei Hsu ; Chihuei Wang ; Chu-I Lee ; Pei-Jung Lu ; Chen-Kung Chou ; Chi-Y
- 刊名：Biochemistry
- 出版年：2006
- 出版时间：September 26, 2006
- 年：2006
- 卷：45
- 期：38
- 页码：11379 - 11389
- 全文大小：626K
- 年卷期：v.45,no.38(September 26, 2006)
- ISSN：1520-4995
文摘
Although prominent FRAT/GBP exhibits a limited degree of homology to Axin, the bindingsites on GSK3 for FRAT/GBP and Axin may overlap to prevent the effect of FRAT/GBP in stabilizing
-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3interaction protein (GSKIP), which binds to GSK3. We have defined a 25-amino acid region in theC-terminus of GSKIP that is highly similar to the GSK3 interaction domain (GID) of Axin. Using an invitro kinase assay, our results indicate that GSKIP is a good GSK3 substrate, and both the full-lengthprotein and a C-terminal fragment of GSKIP can block phosphorylation of primed and nonprimed substratesin different fashions. Similar to Axin GID381-405 and FRATtide, synthesized GSKIPtide is also shown tocompete with and/or block the phosphorylation of Axin and -catenin by GSK3. Furthermore, our dataindicate that overexpression of GSKIP induces -catenin accumulation in the cytoplasm and nucleus asvisualized by immunofluorescence. A functional assay also demonstrates that GSKIP-transfected cellshave a significant effect on the transactivity of Tcf-4. Collectively, we define GSKIP as a naturally occurringprotein that is homologous with the GSK3 interaction domain of Axin and is able to negatively regulateGSK3 of the Wnt signaling pathway.
-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3interaction protein (GSKIP), which binds to GSK3. We have defined a 25-amino acid region in theC-terminus of GSKIP that is highly similar to the GSK3 interaction domain (GID) of Axin. Using an invitro kinase assay, our results indicate that GSKIP is a good GSK3 substrate, and both the full-lengthprotein and a C-terminal fragment of GSKIP can block phosphorylation of primed and nonprimed substratesin different fashions. Similar to Axin GID381-405 and FRATtide, synthesized GSKIPtide is also shown tocompete with and/or block the phosphorylation of Axin and -catenin by GSK3. Furthermore, our dataindicate that overexpression of GSKIP induces -catenin accumulation in the cytoplasm and nucleus asvisualized by immunofluorescence. A functional assay also demonstrates that GSKIP-transfected cellshave a significant effect on the transactivity of Tcf-4. Collectively, we define GSKIP as a naturally occurringprotein that is homologous with the GSK3 interaction domain of Axin and is able to negatively regulateGSK3 of the Wnt signaling pathway.