BCL9-2 binds Arm/beta-catenin in a Tyr142-independent manner and requires Pygopus for its function in Wg/Wnt signaling.
The Wingless (Wg)/Wnt signal transduction pathway controls fundamental processes during animal development. Deregulation of the Wg/Wnt pathway has been causally linked to several forms of cancer, most notably to colorectal cancer. In response to Wg/Wnt signaling, Armadillo/beta-catenin associates in the nucleus with DNA bound TCF and several co-factors, among them ... Legless/BCL9, which provides a link to Pygopus. Recently, the second vertebrate homologue of Legless, BCL9-2 (or B9L), was characterized and proposed to mediate Wnt signaling in a Pygopus-independent manner, by binding to a Tyrosine-142-phosphorylated form of beta-catenin. Here we examine the role of Tyrosine-142 phosphorylation in several assays and find that it is neither important for the recruitment of BCL9-2, nor for the transcriptional activity of beta-catenin in cultured mammalian cells, nor in Drosophila for Wg signaling activity in vivo. Furthermore, we demonstrate that BCL9-2 can functionally replace Lgs both in cultured cells as well as in vivo and that this rescue activity depends on the ability of BCL9-2 to bind Pygo. Our results do not show a significant functional difference between BCL9-2 and BCL9 but rather suggest that the two proteins represent evolutionary duplicates of Legless, which have acquired distinct expression patterns while acting in a largely redundant manner.
Mesh Terms:
Animals, Animals, Genetically Modified, Armadillo Domain Proteins, Base Sequence, Binding Sites, Cell Line, DNA, Drosophila Proteins, Drosophila melanogaster, Evolution, Molecular, Humans, Intracellular Signaling Peptides and Proteins, Mutagenesis, Site-Directed, Neoplasm Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Two-Hybrid System Techniques, Tyrosine, Wnt Proteins, Wnt1 Protein, beta Catenin
Animals, Animals, Genetically Modified, Armadillo Domain Proteins, Base Sequence, Binding Sites, Cell Line, DNA, Drosophila Proteins, Drosophila melanogaster, Evolution, Molecular, Humans, Intracellular Signaling Peptides and Proteins, Mutagenesis, Site-Directed, Neoplasm Proteins, Phosphorylation, Protein Binding, Proto-Oncogene Proteins, Recombinant Proteins, Signal Transduction, Two-Hybrid System Techniques, Tyrosine, Wnt Proteins, Wnt1 Protein, beta Catenin
Mech. Dev.
Date: Jan. 01, 2007
PubMed ID: 17113272
View in: Pubmed Google Scholar
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