GSKIP is homologous to the axin GSK3β interaction domain and functions as a negative regulator of GSK3β

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 Ying Huang, Yi Ren Hong

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)


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 β-catenin in the Wnt pathway. Using a yeast two-hybrid screen, we identified a novel protein, GSK3β interaction protein (GSKIP), which binds to GSK3β. We have defined a 25-amino acid region in the C-terminus of GSKIP that is highly similar to the GSKβ interaction domain (GID) of Axin. Using an in vitro kinase assay, our results indicate that GSKIP is a good GSK3β 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 β-catenin by GSK3β. Furthermore, our data indicate that overexpression of GSKIP induces β-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 GSK3β interaction domain of Axin and is able to negatively regulate GSK3β of the Wnt signaling pathway.

Original languageEnglish
Pages (from-to)11379-11389
Number of pages11
Issue number38
Publication statusPublished - 2006 Sep 26

All Science Journal Classification (ASJC) codes

  • Biochemistry


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