Protein kinase CK2alpha' is induced by serum as a delayed early gene and cooperates with Ha-ras in fibroblast transformation.
Protein kinase CK2 is an ubiquitous and pleiotropic Ser/Thr protein kinase composed of two catalytic (alpha and/or alpha') and two noncatalytic (beta) subunits forming a heterotetrameric holoenzyme involved in cell growth and differentiation. Here we report the identification, cloning, and oncogenic activity of the murine CK2alpha' subunit. Serum treatment of quiescent mouse fibroblasts induces CK2alpha' mRNA expression, which peaks at 4 h. The kinetics of CK2alpha' expression correlate with increased kinase activity toward a specific CK2 holoenzyme peptide substrate. The ectopic expression of CK2alpha' (or CK2alpha) cooperates with Ha-ras in foci formation of rat primary embryo fibroblasts. Moreover, we observed that BALB/c 3T3 fibroblasts transformed with Ha-ras and CK2alpha' show a faster growth rate than cells transformed with Ha-ras alone. In these cells the higher growth rate correlates with an increase in calmodulin phosphorylation, a protein substrate specifically affected by isolated CK2 catalytic subunits but not by CK2 holoenzyme, suggesting that unbalanced expression of a CK2 catalytic subunit synergizes with Ha-ras in cell transformation.
Dipartimento di Biologia Molecolare, Università di Siena IRIS, via Fiorentina 1, 53100 Siena, Italy.
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Orlandini
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Semplici
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Ferruzzi
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Meggio
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Pinna
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Oliviero
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002461:Cell Line, Transformed; D018076:DNA, Complementary; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D017781:Genes, Immediate-Early; D011905:Genes, ras; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009857:Oncogenes; D011493:Protein Kinase C / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D051571:Protein Kinase C-alpha; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D007527:Isoenzymes; D012333:RNA, Messenger; C496628:PRKCA protein, human; C496630:Prkca protein, mouse; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha