Ornithine decarboxylase expression leads to translocation and activation of protein kinase CK2 in vivo.
Ornithine decarboxylase (ODC) is the key initial enzyme in the biosynthesis of polyamines. Since polyamines have been shown to enhance protein kinase CK2 activity in vitro, ODC was overexpressed to examine the role of polyamines in CK2 regulation in vivo. Infection of Balb/MK cells with an ODC retrovirus to elevate ODC and polyamine levels increased overall protein phosphorylation as well as CK2 protein levels and enzyme activity in mimosine- or nocodazole- arrested cells. Immunofluorescence microscopy and enzyme analyses of subcellular fractions from ODC-overexpressing cells demonstrated translocation of CK2 from the cytoplasm to the nucleus with no apparent loss of cytoplasmic CK2 activity, suggesting polyamine activation of the remaining cytoplasmic enzyme. Similarly, K6/ODC transgenic mice exhibited higher ODC and CK2 enzyme activities than their normal littermates. ODC-immunostained cells in the transgenic skin also stained intensely for CK2 protein. Primary cultures of K6/ODC keratinocytes also exhibited increased ODC and CK2 enzyme activities compared with those from normal littermates. However, the addition of difluoromethylornithine, a specific ODC inhibitor, to the transgenic keratinocytes reduced both intracellular polyamine levels and CK2 enzyme activity. These results suggest that polyamines regulate the CK2 enzyme by affecting its cellular distribution as well as its enzyme activity and levels.
Shore
L J
LJ
Lankenau Medical Research Center, Wynnewood, Pennsylvania 19096, USA.
Soler
A P
AP
Gilmour
S K
SK
D000818:Animals; D047390:Casein Kinase II; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004789:Enzyme Activation; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D009570:Nitriles / Q000378:metabolism; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000378:metabolism
D004268:DNA-Binding Proteins; D009570:Nitriles; D011073:Polyamines; D011726:Pyridinium Compounds; C067292:1-cyano-4-dimethylaminopyridinium; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D009955:Ornithine Decarboxylase