Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and β-catenin

Keiji Itoh, Valery E. Krupnik, Sergei Y. Sokol

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

Signaling by the Wnt family of extracellular proteins is critical in a variety of developmental processes in which cell and tissue polarity are established [1-5]. Wnt signal transduction has been studied mostly by the genetic approach in Drosophila and Caenorhabditis elegans [12,5], but the biochemical mechanisms involved remain to be elucidated. The Wnt pathway also operates during axis determination in vertebrates [3,5]. Frizzled receptors transduce a signal to Dishevelled, leading to inactivation of glycogen synthase kinase 3 (GSK3) and regulation of gene expression by the complex of β-catenin with LEF/TCF (lymphocyte enhancer factor/T-cell factor) transcription factors [3,5]. Axin is a negative regulator of wnt signaling and dorsal axial development in vertebrates [6]. Here, we demonstrate that axin is associated with GSK3 in the Xenopus embryo and we localize the GSK3-binding domain to a short region of axin. Binding of GSK3 correlates with the ability of axin to inhibit axial development and with the axis-inducing activity of its dominant-negative form (ΔRGS). We also find that wild-type axin, but not ΔRGS, forms a complex with β-catenin. Thus, axin may act as a docking station mediating negative regulation of β-catenin by GSK3 during dorsoventral axis determination in vertebrate embryos.

Original languageEnglish
Pages (from-to)591-594
Number of pages4
JournalCurrent Biology
Volume8
Issue number10
DOIs
StatePublished - 7 May 1998
Externally publishedYes

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