Domains of Axin Involved in Protein–Protein Interactions, Wnt Pathway Inhibition, and Intracellular Localization
Open Access
- 17 May 1999
- journal article
- Published by Rockefeller University Press in The Journal of cell biology
- Vol. 145 (4), 741-756
- https://doi.org/10.1083/jcb.145.4.741
Abstract
Axin was identified as a regulator of embryonic axis induction in vertebrates that inhibits the Wnt signal transduction pathway. Epistasis experiments in frog embryos indicated that Axin functioned downstream of glycogen synthase kinase 3β (GSK3β) and upstream of β-catenin, and subsequent studies showed that Axin is part of a complex including these two proteins and adenomatous polyposis coli (APC). Here, we examine the role of different Axin domains in the effects on axis formation and β-catenin levels. We find that the regulators of G-protein signaling domain (major APC-binding site) and GSK3β-binding site are required, whereas the COOH-terminal sequences, including a protein phosphatase 2A binding site and the DIX domain, are not essential. Some forms of Axin lacking the β-catenin binding site can still interact indirectly with β-catenin and regulate β-catenin levels and axis formation. Thus in normal embryonic cells, interaction with APC and GSK3β is critical for the ability of Axin to regulate signaling via β-catenin. Myc-tagged Axin is localized in a characteristic pattern of intracellular spots as well as at the plasma membrane. NH2-terminal sequences were required for targeting to either of these sites, whereas COOH-terminal sequences increased localization at the spots. Coexpression of hemagglutinin-tagged Dishevelled (Dsh) revealed strong colocalization with Axin, suggesting that Dsh can interact with the Axin/APC/GSK3/β-catenin complex, and may thus modulate its activity.Keywords
This publication has 52 references indexed in Scilit:
- Axis determination in Xenopus involves biochemical interactions of axin, glycogen synthase kinase 3 and β-cateninCurrent Biology, 1998
- Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3βCurrent Biology, 1998
- Functional Interaction of an Axin Homolog, Conductin, with β-Catenin, APC, and GSK3βScience, 1998
- Signal transduction through beta-catenin and specification of cell fate during embryogenesis.Genes & Development, 1996
- A frizzled homolog functions in a vertebrate Wnt signaling pathwayCurrent Biology, 1996
- Binding of GSK3β to the APC-β-Catenin Complex and Regulation of Complex AssemblyScience, 1996
- Cell adhesion and signal transduction: the Armadillo connectionTrends in Cell Biology, 1995
- Mutations in the APC gene and their implications for protein structure and functionCurrent Opinion in Genetics & Development, 1995
- Spatial expression of the Drosophila segment polarity gene armadillo is posttranscriptionally regulated by winglessCell, 1990
- The entire mesodermal mantle behaves as Spemann's organizer in dorsoanterior enhanced Xenopus laevis embryosDevelopmental Biology, 1988