Activation of protein kinase Cdelta in human myeloid leukemia cells treated with 1-beta-D-arabinofuranosylcytosine.
Treatment of human myeloid leukemia cells with 1-beta-D-arabinofuranosylcytosine (ara-C) is associated with induction of protein kinase activity and early-response gene expression. The present studies in ara-C-treated U-937 cells extend these findings by demonstrating activation of a protein kinase that phosphorylates myelin basic protein (MBP). Purification by sequential ion-exchange chromatography and gel filtration supports the detection of a 40-kD MBP kinase. Substrate and inhibitor studies further support a pattern similar to that of protein kinase C (PKC) isozymes. Results of N-terminal amino acid sequencing and immunoblot analysis demonstrate detection of a 40-kD catalytic fragment of PKCdelta. The results also demonstrate the activation and cleavage of PKCdelta (1) is inhibited by expression of antiapoptotic proteins, and (2) is induced by camptothecin (CAM) and mitomycin C (MMC). These findings support proteolytic activation of PKCdelta in the cellular response to ara-C and other DNA-damaging agents.
Emoto
Y
Y
Division of Cancer Pharmacology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Kisaki
H
H
Manome
Y
Y
Kharbanda
S
S
Kufe
D
D
D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000494:pharmacology; D003561:Cytarabine / Q000494:pharmacology*; D004249:DNA Damage; D010450:Endopeptidases / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D016758:Genes, jun; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes / Q000378:metabolism*; D007951:Leukemia, Myeloid / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D008565:Membrane Proteins; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D004676:Myelin Basic Protein / Q000378:metabolism; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009363:Neoplasm Proteins / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000187:drug effects* / Q000201:enzymology; D009707:Nucleosomes / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D051745:Protein Kinase C-delta; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D011506:Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013379:Substrate Specificity; D014407:Tumor Cells, Cultured
D047908:Intracellular Signaling Peptides and Proteins; D007527:Isoenzymes; D008565:Membrane Proteins; D004676:Myelin Basic Protein; D009363:Neoplasm Proteins; D009707:Nucleosomes; D011506:Proteins; D003561:Cytarabine; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D016685:Mitomycin; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta; D010450:Endopeptidases; D002166:Camptothecin