Regulation of c-myc and ornithine decarboxylase expression by distinct protein kinase systems in IL-3-dependent myeloid cells.
We have investigated whether PK-C-regulated events are independent of those biochemical events related to IL-3-induced tyrosine kinase activation by 32Dcl cells. The depletion of functional PK-C isoform activity by prolonged PMA treatment reduced the proliferative response to IL-3 by half that of untreated control cells. PK-C-deficient 32Dcl cells were unable to respond to PMA for the induction of c-myc and ODC mRNA accumulation. PK-C down-regulation did not affect IL-3-induced tyrosine phosphorylation and inhibited IL-3-regulated c-myc and ODC mRNA expression by only 30%. However, PK-C down-regulation had a pronounced inhibitory effect on IL-3 regulation of ODC enzymatic activity. While a PK-C-dependent and -independent pathway for the regulation of c-myc and ODC mRNA expression could be demonstrated, the regulation of ODC enzymatic activity appeared to require an intact PK-C system. The data suggest that the optimum biological and biochemical responses to IL-3 requires both pathways intact, however, tyrosine kinase activation and significant increases in gene products associated with proliferation can be achieved in the absence of a functional PK-C system.
Farrar
W L
WL
Cytokine Molecular Mechanisms Section, National Cancer Institute-Frederick Cancer Research and Development Center, MD 21702-1201.
Willette-Brown
J
J
Linnekin
D
D
D000818:Animals; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D015536:Down-Regulation / Q000187:drug effects; D015870:Gene Expression; D016259:Genes, myc; D006412:Hematopoietic Stem Cells / Q000502:physiology*; D066298:In Vitro Techniques; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000235:genetics*; D019000:Phosphotyrosine; D011493:Protein Kinase C / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
D007377:Interleukin-3; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D019000:Phosphotyrosine; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate