Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells

Citation
Dh. Song et al., Endogenous protein kinase CK2 participates in Wnt signaling in mammary epithelial cells, J BIOL CHEM, 275(31), 2000, pp. 23790-23797
Citations number
81
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
00219258 → ACNP
Volume
275
Issue
31
Year of publication
2000
Pages
23790 - 23797
Database
ISI
SICI code
0021-9258(20000804)275:31<23790:EPKCPI>2.0.ZU;2-V
Abstract
Protein kinase CK2 (formerly casein kinase II) is a serine/threonine kinase overexpressed in many human tumors, transformed cell lines, and rapidly pr oliferating tissues. Recent data have shown that many cancers involve inapp ropriate reactivation of Wnt signaling through ectopic expression of Wnts t hemselves, as has been seen in a number of human breast cancers, or through mutation of intermediates in the Wnt pathway, such as adenomatous polyposi s coli or beta-catenin, as described in colon and other cancers. Wnts are s ecreted factors that are important in embryonic development, but overexpres sion of certain Wnts, such as Wnt-1, leads to proliferation and transformat ion of cells. We report that upon stable transfection of Wnt-1 into the mou se mammary epithelial cell line C57MG, morphological changes and increased proliferation are accompanied by increased levels of CK2, as well as of bet a-catenin, CK2 and beta-catenin co-precipitate with the Dvl proteins, which are Wnt signaling intermediates. A major phosphoprotein of the size of bet a-catenin appears in in vitro kinase reactions performed on the Dvl immunop recipitates. In vitro translated beta-catenin, Dvl-2, and Dvl-3 are phospho rylated by CK2. The selective CK2 inhibitor apigenin blocks proliferation o f Wnt-1-transfected cells, abrogates phosphorylation of beta-catenin, and r educes beta-catenin and Dvl protein levels. These results demonstrate that endogenous CK2 is a positive regulator of Wnt signaling and growth of mamma ry epithelial cells.