Wnt signaling: Axin--More Than a Scaffold

Glycogen synthase kinase 3beta (GSK-3beta) is a negative regulator of the Wnt signaling pathway, which is important for vertebrate axis formation during development. Axin binds beta-catenin and GSK-3beta, and facilitates phosphorylation of beta-catenin by the enzyme. This event is inhibitory to Wnt signaling. Hedgepeth et al. now show that in unlike full-length axin, which inhibits Wnt siganling, a 25 amino acid region in Axin can bind to GSK-3beta and inhibit its enzyme activity, thus activating the Wnt signaling pathway in Xenopus embryos. The authors have also identified a region in Axin that mediates interaction with other axin molecules. The authors suggest that axin complex formation may be necessary to maintain GSK-3b activity. Furthermore, in addition to its proposed role as an scaffold protein and antagonist of Wnt signaling, axin may also regulate Wnt signaling by directly inhibiting GSK-3beta. Hedgepeth, C.M., Deardorff, M.A., Rankin, K., and Klein, P.S. (1999) Regulation of glycogen synthase kinase 3b and downstream Wnt signaling by axin. Mol. Cell. Biol. 19 : 7147-7157. [Abstract]