Regulation of beta-catenin function by the IkappaB kinases.
Both the beta-catenin and the nuclear factor kappaB (NF-kappaB) proteins are important regulators of gene expression and cellular proliferation. Two kinases, IKKalpha and IKKbeta, are critical activators of the NF-kappaB pathway. Here we present evidence that these kinases are also important in the regulation of beta-catenin function. IKKalpha- and IKKbeta-deficient ... mouse embryo fibroblasts exhibited different patterns of beta-catenin cellular localization. IKKbeta decreases beta-catenin-dependent transcriptional activation, while IKKalpha increases beta-catenin-dependent transcriptional activity. IKKalpha and IKKbeta interact with and phosphorylate beta-catenin using both in vitro and in vivo assays. Our results suggest that differential interactions of beta-catenin with IKKalpha and IKKbeta may in part be responsible for regulating beta-catenin protein levels and cellular localization and integrating signaling events between the NF-kappaB and Wingless pathways.
Mesh Terms:
Animals, COS Cells, Cytoskeletal Proteins, I-kappa B Kinase, Mice, NF-kappa B, Phosphorylation, Protein-Serine-Threonine Kinases, Trans-Activators, Transcriptional Activation, Tumor Necrosis Factor-alpha, beta Catenin
Animals, COS Cells, Cytoskeletal Proteins, I-kappa B Kinase, Mice, NF-kappa B, Phosphorylation, Protein-Serine-Threonine Kinases, Trans-Activators, Transcriptional Activation, Tumor Necrosis Factor-alpha, beta Catenin
J. Biol. Chem.
Date: Nov. 09, 2001
PubMed ID: 11527961
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