Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells.
Protein kinase CK2 (formerly casein kinase II) is a serine/threonine kinase overexpressed in many human tumors, transformed cell lines, and rapidly proliferating tissues. Recent data have shown that many cancers involve inappropriate reactivation of Wnt signaling through ectopic expression of Wnts themselves, as has been seen in a number of human breast cancers, or through mutation of intermediates in the Wnt pathway, such as adenomatous polyposis coli or beta-catenin, as described in colon and other cancers. Wnts are secreted factors that are important in embryonic development, but overexpression of certain Wnts, such as Wnt-1, leads to proliferation and transformation of cells. We report that upon stable transfection of Wnt-1 into the mouse mammary epithelial cell line C57MG, morphological changes and increased proliferation are accompanied by increased levels of CK2, as well as of beta-catenin. CK2 and beta-catenin co-precipitate with the Dvl proteins, which are Wnt signaling intermediates. A major phosphoprotein of the size of beta-catenin appears in in vitro kinase reactions performed on the Dvl immunoprecipitates. In vitro translated beta-catenin, Dvl-2, and Dvl-3 are phosphorylated by CK2. The selective CK2 inhibitor apigenin blocks proliferation of Wnt-1-transfected cells, abrogates phosphorylation of beta-catenin, and reduces beta-catenin and Dvl protein levels. These results demonstrate that endogenous CK2 is a positive regulator of Wnt signaling and growth of mammary epithelial cells.
Song
D H
DH
Departments of Medicine, Chemistry, and Microbiology, Boston Medical Center and Boston University, Boston, Massachusetts 02118, USA.
Sussman
D J
DJ
Seldin
D C
DC
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D047310:Apigenin; D047390:Casein Kinase II; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000378:metabolism; D000072261:Dishevelled Proteins; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D005419:Flavonoids / Q000494:pharmacology; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D008934:Mitogens / Q000378:metabolism; D008957:Models, Genetic; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015534:Trans-Activators; D014162:Transfection; D015854:Up-Regulation; D051153:Wnt Proteins; D051155:Wnt1 Protein; D029961:Zebrafish Proteins; D051176:beta Catenin
D048868:Adaptor Proteins, Signal Transducing; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; C000606581:DVL2 protein, human; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; C000606582:Dvl2 protein, mouse; C000606585:Dvl3 protein, mouse; D005419:Flavonoids; D008934:Mitogens; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D051155:Wnt1 Protein; C495246:Wnt1 protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin; D047310:Apigenin; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases