Interleukin-3 and phorbol esters induce different patterns of immediate-early gene expression in an interleukin-3 dependent cell line.
The myeloid interleukin-3 (IL-3) dependent cell line, FDC-P1, enters the G0 stage of the cell cycle after IL-3 deprivation for 24 hr. The expression of 13 protooncogenes and immediate-early genes was compared with 4 "control" genes after the addition of either IL-3 or phorbol myristate acetate (PMA) to IL-3-deprived cells. mRNA transcripts encoding c-myc and the T-cell receptor c-gamma gene were induced to high levels only after IL-3 addition, whereas c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 were induced transiently only after PMA addition. The remaining genes (fra-1, p53, jun-D, c-Ha-ras, c-Ki-ras, c-raf, beta-actin, ornithine decarboxylase, and histone 2B) were detected after culture with either IL-3 or PMA. When cells were serum- and IL-3-deprived, c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 were detected after exposure to either serum or PMA. Moreover, culture with cycloheximide and PMA resulted in superinduction of these genes, whereas cycloheximide and IL-3 addition did not. mRNAs encoding these genes had half-lives of 10-20 min after PMA treatment, whereas that of beta-actin was longer (greater than 2 hr), suggesting that short mRNA half-lives contributed to the transient nature of these genes. Although c-fos, fos-B, c-jun, jun-B, Krox-20, and Krox-24 expression can be detected in IL-3-dependent cells after exposure to either PMA or serum, these genes were not detected after IL-3 addition, which allows cell-cycle progression. These results document the existence of IL-3 and PMA-responsive genes and demonstrate that IL-3 and protein kinase C agonists can induce distinct patterns of gene expression.
McCubrey
J A
JA
Department of Microbiology & Immunology, East Carolina University School of Medicine, Greenville, North Carolina 27858.
Steelman
L S
LS
McKearn
J P
JP
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins; D015152:Blotting, Northern; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D003609:Dactinomycin / Q000494:pharmacology; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; D005786:Gene Expression Regulation / Q000187:drug effects*; D011905:Genes, ras / Q000187:drug effects; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006207:Half-Life; D006657:Histones / Q000096:biosynthesis; D017874:Immediate-Early Proteins; D007377:Interleukin-3 / Q000494:pharmacology*; D051379:Mice; D009955:Ornithine Decarboxylase / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D019908:Proto-Oncogene Proteins c-raf; D012313:RNA / Q000096:biosynthesis; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016692:Receptors, Antigen, T-Cell, gamma-delta; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014157:Transcription Factors / Q000096:biosynthesis; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis
D000199:Actins; D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D051766:Early Growth Response Protein 1; D051767:Early Growth Response Protein 2; C486109:Egr1 protein, mouse; C497327:Egr2 protein, mouse; C483819:Fosb protein, mouse; D006657:Histones; D017874:Immediate-Early Proteins; D007377:Interleukin-3; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D003609:Dactinomycin; D012313:RNA; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D003513:Cycloheximide; D019908:Proto-Oncogene Proteins c-raf; D009955:Ornithine Decarboxylase; D013755:Tetradecanoylphorbol Acetate