Tyrosine phosphorylation is a mandatory proximal step in radiation-induced activation of the protein kinase C signaling pathway in human B-lymphocyte precursors.
Ionizing radiation triggers a signal in human B-lymphocyte precursors that is intimately linked to an active protein-tyrosine kinase regulatory pathway. We show that in B-lymphocyte precursors, irradiation with gamma-rays leads to (i) stimulation of phosphatidylinositol turnover; (ii) downstream activation by covalent modification of multiple serine-specific protein kinases, including protein kinase C; and (iii) activation of nuclear factor kappa B. All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herbimycin A. Thus, tyrosine phosphorylation is an important and perhaps mandatory proximal step in the activation of the protein kinase C signaling cascade in human B-lymphocyte precursors. Our report expands current knowledge of the radiation-induced signaling cascade by clarifying the chronological sequence of biochemical events that follow irradiation.
Uckun
F M
FM
Department of Therapeutic Radiology-Radiation Oncology, University of Minnesota, Minneapolis 55455.
Schieven
G L
GL
Tuel-Ahlgren
L M
LM
Dibirdik
I
I
Myers
D E
DE
Ledbetter
J A
JA
Song
C W
CW
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D001402:B-Lymphocytes / Q000528:radiation effects*; D016227:Benzoquinones; D002460:Cell Line; D002588:Cesium Radioisotopes; D004307:Dose-Response Relationship, Radiation; D004789:Enzyme Activation; D005720:Gamma Rays; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D047029:Lactams, Macrocyclic; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism* / Q000528:radiation effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000528:radiation effects; D011809:Quinones / Q000494:pharmacology; D017828:Rifabutin / Q000031:analogs & derivatives; D015398:Signal Transduction / Q000528:radiation effects*; D014407:Tumor Cells, Cultured
D016227:Benzoquinones; D002588:Cesium Radioisotopes; D007546:Isoquinolines; D047029:Lactams, Macrocyclic; D016328:NF-kappa B; D010879:Piperazines; D011809:Quinones; D017828:Rifabutin; C020754:herbimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D015544:Inositol 1,4,5-Trisphosphate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C