Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Copyright policy )Control of β-Catenin Phosphorylation/Degradation by a Dual-Kinase Mechanism
Wnt regulation of beta-catenin degradation is essential for development and carcinogenesis. beta-catenin degradation is initiated upon amino-terminal serine/threonine phosphorylation, which is believed to be performed by glycogen synthase kinase-3 (GSK-3) in complex with tumor suppressor proteins Axin and adnomatous polyposis coli (APC). Here we describe another Axin-associated kinase, whose phosphorylation of beta-catenin precedes and is required for subsequent GSK-3 phosphorylation of beta-catenin. This "priming" kinase is casein kinase Ialpha (CKIalpha). Depletion of CKIalpha inhibits beta-catenin phosphorylation and degradation and causes abnormal embryogenesis associated with excessive Wnt/beta-catenin signaling. Our study uncovers distinct roles and steps of beta-catenin phosphorylation, identifies CKIalpha as a component in Wnt/beta-catenin signaling, and has implications to pathogenesis/therapeutics of human cancers and diabetes.
- Boston Children's Hospital United States
- Harvard University United States
- Sanford Burnham Prebys Medical Discovery Institute United States
Armadillo Domain Proteins, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Glycogen Synthase Kinases, Gene Expression, Cell Line, Enzyme Activation, Cytoskeletal Proteins, Glycogen Synthase Kinase 3, Axin Protein, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Drosophila Proteins, Humans, Insect Proteins, Drosophila, Amino Acid Sequence, Phosphorylation, Casein Kinases, Protein Kinases, Body Patterning
Armadillo Domain Proteins, Biochemistry, Genetics and Molecular Biology(all), Molecular Sequence Data, Glycogen Synthase Kinases, Gene Expression, Cell Line, Enzyme Activation, Cytoskeletal Proteins, Glycogen Synthase Kinase 3, Axin Protein, Calcium-Calmodulin-Dependent Protein Kinases, Animals, Drosophila Proteins, Humans, Insect Proteins, Drosophila, Amino Acid Sequence, Phosphorylation, Casein Kinases, Protein Kinases, Body Patterning
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