Cyclin-dependent kinase 2 regulates the interaction of Axin with beta-catenin.
Axin, a negative regulator of Wnt, forms a complex with glycogen synthase kinase 3beta, beta-catenin, and adenomatous polyposis coli and promotes GSK3beta-dependent phosphorylation of beta-catenin, thereby stimulating degradation of the beta-catenin. An essential step in that process is the phosphorylation of Axin. Examination of Axin's amino acid sequence revealed it to contain six arginine-X-leucine (RXL) sequences, the cyclin-dependent kinase 2 (CDK2) binding motif, and 10 CDK2 consensus phosphorylation sequences. We also found that cyclin A/CDK2 phosphorylates Axin, thereby enhancing its association with beta-catenin. This suggests that cyclin A/CDK2 is a negative regulator of beta-catenin-mediated signal transduction, which exerts its effects through phosphorylation of Axin.
Kim
Sung Il
SI
Department of Life Science, Kwangju Institute of Science and Technology, Kwangju 500-712, Republic of Korea.
Park
Chun Shik
CS
Lee
Mi Su
MS
Kwon
Min Seong
MS
Jho
Eek-hoon
EH
Song
Woo Keun
WK
D000818:Animals; D060466:Axin Protein; D001665:Binding Sites; D042846:CDC2-CDC28 Kinases / Q000737:chemistry* / Q000378:metabolism*; D019556:COS Cells; D002384:Catalysis; D002522:Chlorocebus aethiops; D051357:Cyclin-Dependent Kinase 2; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats; D012097:Repressor Proteins / Q000737:chemistry* / Q000378:metabolism*; D015534:Trans-Activators / Q000737:chemistry* / Q000378:metabolism*; D051176:beta Catenin
D060466:Axin Protein; C495270:CTNNB1 protein, human; C495268:Ctnnb1 protein, rat; D003598:Cytoskeletal Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495892:Cdk2 protein, rat; D051357:Cyclin-Dependent Kinase 2