Cyclic adenosine 3':5'-monophosphate-dependent and -independent protein kinase in acute myeloblastic leukemia.
Determination of levels and isozymic patterns of protein kinase activities was performed upon extracts from two human leukemia cell lines (K562 and HL-60) and blast cells from five untreated patients with acute myeloblastic leukemia and compared to activities from normal human peripheral blood granulocytes and bone marrow samples enriched for proliferative myeloid cells. The leukemic cells studied were found to have higher specific activities of cytosol cyclic adenosine 3':5'-monophosphate (cAMP)-independent casein kinase and lower activation by cAMP of their cytosol histone kinase compared to the normal myeloid cells studied. Diethylaminoethyl-cellulose chromatography revealed correspondingly higher amounts of cAMP-independent protein kinase isoenzymes (two casein kinase and one histone kinase peaks) in the leukemic cells, as well as altered ratios of the two cAMP-dependent isozymes. Casein phosphorylating activities extracted from the nuclei of the leukemic cell lines were also high compared to normal myeloid cells. Further purification and estimation of molecular weights of the isoenzymes present in leukemia were accomplished by gel filtration, using Sephacryl S-200. Resolution of the acute myeloblastic leukemia cell line nuclear casein kinase activity into two peaks was also thereby accomplished. The nuclear peaks eluted earlier than the corresponding cytoplasmic peaks; thus, the nuclear isoenzymes may not be identical to those from the cytoplasm. The increased protein kinase activity noted in such cells may be an important biochemical concomitant of transformation.
D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D002848:Chromatography, DEAE-Cellulose; D002850:Chromatography, Gel; D000242:Cyclic AMP / Q000494:pharmacology*; D003600:Cytosol / Q000201:enzymology; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000201:enzymology*; D011494:Protein Kinases / Q000378:metabolism*
D007527:Isoenzymes; D000242:Cyclic AMP; D011494:Protein Kinases