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Wnt signaling: Axin--More Than a Scaffold

Science's STKE  12 Oct 1999:
Vol. 1999, Issue 3, pp. tw3
DOI: 10.1126/stke.1999.3.tw3

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]