Tyrosine Phosphorylation is a Mandatory Proximal Step in Radiation-Induced Activation of the Protein Kinase C Signaling Pathway in Human B-Lymphocyte Precursors

• Published in: Proceedings of the National Academy of Sciences - PNAS 1993-01, Vol.90 (1), p.252-256
• Main Authors: Uckun, Fatih M., Schieven, Gary L., Tuel-Ahlgren, Lisa M., Dibirdik, Ilker, Myers, Dorothea E., Ledbetter, Jeffrey A., Song, Chang W.
• Format: Article
• Language: English
• Subjects: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; B lymphocytes; B-Lymphocytes - radiation effects; Benzoquinones; Biological and medical sciences; Cell Line; Cell lines; Cellular immunity; Cesium Radioisotopes; Dose-Response Relationship, Radiation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Fundamental immunology; Gamma Rays; Gels; Humans; Immunobiology; Inositol 1,4,5-Trisphosphate - metabolism; Ionizing radiation; Irradiation; Isoquinolines - pharmacology; Kinetics; Lactams, Macrocyclic; Lymphocytes; Lymphoid cells: ontogeny, maturation, markers, receptors, circulation and recirculation; Medical research; NF-kappa B - metabolism; Phosphorylation; Piperazines - pharmacology; Protein Kinase C - metabolism; Protein Kinase C - radiation effects; Protein precursors; Protein-Tyrosine Kinases - antagonists & inhibitors; Protein-Tyrosine Kinases - metabolism; Protein-Tyrosine Kinases - radiation effects; Quinones - pharmacology; Radiation; Rifabutin - analogs & derivatives; Signal Transduction - radiation effects; Stem cells; Tumor Cells, Cultured
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.90.1.252

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 γ-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 κ B. All of the radiation-induced signals were effectively prevented by the protein-tyrosine kinase inhibitors genistein and herhimycin 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.