title: Role of hydroxyl radicals in radiation-induced activation of lyn tyrosine kinase in human B-cell precursors.
abstract: Here we show that exposure of human B-cell precursors to gamma-rays stimulates the enzymatic activity of the Src protooncogene family protein tyrosine kinase LYN. LYN activation in irradiated cells is not triggered by DNA damage or a nuclear signal since gamma-rays effectively stimulated LYN kinase in enucleated B-cell precursors as well. LYN activation in irradiated cells was abrogated by presence of the OH* radical scavenger dimethylsulfoxide and exposure of intact or enucleated B-cell precursors to chemically generated OH* radicals instead of gamma-rays also triggered LYN kinase activation and enhanced tyrosine phosphorylation of multiple electrophoretically distinct protein substrates. Thus, OH* radicals appear to be both mandatory and sufficient for radiation-induced LYN kinase activation in irradiated B-cell precursors. We further present evidence which indicates that OH* radicals activate LYN by a novel mechanism which involves disruption of inactive LYN-LYN homodimers and monomerization of the LYN kinase after proteolytic degradation of a putative LYN-associated adapter protein through a cytoplasmic TPCK-sensitive chymotrypsin-like protease following its oxidation. LYN kinase plays a pivotal role in initiation of signal cascades that affect the proliferation, differentiation, and survival of B-cell precursors. Our results prompt the hypothesis that a growth regulatory balance might be altered in human B-cell precursors by radiation-induced stimulation of LYN kinase.
authors.affiliation: Dept. of Therapeutic Radiology-Radiation Oncology, University of Minnesota Health Sciences Center, USA.
authors.forename: J
authors.initials: J
authors.lastname: Xiao
authors.forename: J E
authors.initials: JE
authors.lastname: Biaglow
authors.forename: H J
authors.initials: HJ
authors.lastname: Chae-Park
authors.forename: J
authors.initials: J
authors.lastname: Jin
authors.forename: L
authors.initials: L
authors.lastname: Tuel-Ahlgren
authors.forename: D E
authors.initials: DE
authors.lastname: Myers
authors.forename: A L
authors.initials: AL
authors.lastname: Burkhardt
authors.forename: J B
authors.initials: JB
authors.lastname: Bolen
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D001402:B-Lymphocytes / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects*; D002460:Cell Line; D004789:Enzyme Activation; D005720:Gamma Rays; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D019000:Phosphotyrosine / Q000032:analysis; D011480:Protease Inhibitors / Q000494:pharmacology; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism; D014108:Tosylphenylalanyl Chloromethyl Ketone / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D019061:src-Family Kinases / Q000378:metabolism* / Q000528:radiation effects
chemical_list: D011480:Protease Inhibitors; D019000:Phosphotyrosine; D017665:Hydroxyl Radical; D014108:Tosylphenylalanyl Chloromethyl Ketone; D019061:src-Family Kinases; D017027:Protein Tyrosine Phosphatases