Axin, a negative regulator of the wnt signaling pathway, directly interacts with adenomatous polyposis coli and regulates the stabilization of beta-catenin.
The regulators of G protein signaling (RGS) domain of Axin, a negative regulator of the Wnt signaling pathway, made a complex with full-length adenomatous polyposis coli (APC) in COS, 293, and L cells but not with truncated APC in SW480 or DLD-1 cells. The RGS domain directly interacted with the region containing the 20-amino acid repeats but not with that containing the 15-amino acid repeats of APC, although both regions are known to bind to beta-catenin. In the region containing seven 20-amino acid repeats, the region containing the latter five repeats bound to the RGS domain of Axin. Axin and beta-catenin simultaneously interacted with APC. Furthermore, Axin stimulated the degradation of beta-catenin in COS cells. Taken together with our recent observations that Axin directly interacts with glycogen synthase kinase-3beta (GSK-3beta) and beta-catenin and that it promotes GSK-3beta-dependent phosphorylation of beta-catenin, these results suggest that Axin, APC, GSK-3beta, and beta-catenin make a tetrameric complex, resulting in the regulation of the stabilization of beta-catenin.
Kishida
S
S
Department of Biochemistry, Hiroshima University School of Medicine, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan.
Yamamoto
H
H
Ikeda
S
S
Kishida
M
M
Sakamoto
I
I
Koyama
S
S
Kikuchi
A
A
D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D060466:Axin Protein; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D006801:Humans; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012097:Repressor Proteins; D015398:Signal Transduction; D015534:Trans-Activators; D051176:beta Catenin
D025601:Adenomatous Polyposis Coli Protein; D060466:Axin Protein; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D015534:Trans-Activators; D051176:beta Catenin