To explore more possible roles for GSK3 beta function, the yeast two-hybrid screening using GSK3 beta as a bait protein was performed. In this study, we demonstrated that two variants of CABYR (281 and 379) interacted with GSK3 beta in the yeast two-hybrid and GST pull down assay. Molecular characterization showed that CABYR variants formed a dimer with a proline-rich extensin-like domain, which slightly overlapped with GSK3 beta-binding site. In kinase assay, we also showed that CABYR variants act as an ideal substrate for GSK3 beta within the extensin-like domain and phosphorylation sites on CABYR were mapped. Interestingly, Northern blot showed that CABYR transcripts were expressed more distinctly in the fetal brain than in the adult brain, suggesting that this protein may play a role during brain development. Moreover, differential expression of CABYR variants may exhibit aberrant expression in brain tumors and cancer cell lines. (c) 2005 Elsevier Inc. All rights reserved.