Early response gene signalling cascades activated by ionising radiation in primary human B cells.
We have used a panel of 13 protein kinase C-responsive immediate early gene probes to dissect the cellular signalling pathways activated by ionising gamma radiation in primary human B cells. Of these 13 genes, a delayed transient induction was observed for only 8: c-fos, c-jun, jun-B, jun-D, c-myc, ergI/krox 24 and two 'anonymous' genes, 3L3 and 19A. Expression of c-myc and c-fos mRNAs was paralleled by the appearance of their encoded proteins suggesting that these oncoproteins may couple radiation signalling to cellular responses. Of three protein kinase C-coupled transcription factors examined by gel retardation assay, (AP1, NF kappa B, EgrK/Krox24) only NF kappa B and, to a lesser extent, AP1 was stimulated in response to irradiation. These observations are not obviously compatible with a simple model invoking protein kinase C in radiation signalling in primary B cells and suggest that the pleiotropic effects of ionising radiation on this cell type are mediated through a distinct cellular signalling cascade.
Wilson
R E
RE
CRC Department of Carcinogenesis, Paterson Institute for Cancer Research, Christie Hospital NHS Trust, Manchester, UK.
Taylor
S L
SL
Atherton
G T
GT
Johnston
D
D
Waters
C M
CM
Norton
J D
JD
D001402:B-Lymphocytes / Q000737:chemistry / Q000166:cytology* / Q000528:radiation effects*; D001483:Base Sequence; D015152:Blotting, Northern; D015153:Blotting, Western; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051766:Early Growth Response Protein 1; D005786:Gene Expression Regulation / Q000235:genetics / Q000528:radiation effects*; D017781:Genes, Immediate-Early / Q000235:genetics* / Q000528:radiation effects*; D006801:Humans; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis / Q000235:genetics / Q000502:physiology; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D011839:Radiation, Ionizing; D015682:Retroviridae Proteins, Oncogenic / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects
D004268:DNA-Binding Proteins; C497325:EGR1 protein, human; D051766:Early Growth Response Protein 1; D017874:Immediate-Early Proteins; D016328:NF-kappa B; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015682:Retroviridae Proteins, Oncogenic; D014157:Transcription Factors; D004247:DNA; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate