title: Role of tyrosine kinases in induction of the c-jun proto-oncogene in irradiated B-lineage lymphoid cells.
abstract: Exposure of B-lineage lymphoid cells to ionizing radiation induces an elevation of c-jun proto-oncogene mRNA levels. This signal is abrogated by protein-tyrosine kinase (PTK) inhibitors, indicating that activation of an as yet unidentified PTK is mandatory for radiation-induced c-jun expression. Here, we provide experimental evidence that the cytoplasmic tyrosine kinases BTK, SYK, and LYN are not required for this signal. Lymphoma B-cells rendered deficient for LYN, SYK, or both by targeted gene disruption showed increased c-jun expression levels after radiation exposure, but the magnitude of the stimulation was lower than in wild-type cells. Thus, these PTKs may participate in the generation of an optimal signal. Notably, an inhibitor of JAK-3 (Janus family kinase-3) abrogated radiation-induced c-jun activation, prompting the hypothesis that a chicken homologue of JAK-3 may play a key role in initiation of the radiation-induced c-jun signal in B-lineage lymphoid cells.
authors.affiliation: Department of Molecular Genetics, Wayne Hughes Institute, St. Paul, Minnesota 55113, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Goodman
authors.forename: L B
authors.initials: LB
authors.lastname: Niehoff
authors.forename: F M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology / Q000378:metabolism* / Q000528:radiation effects; D001483:Base Sequence; D002460:Cell Line; D002645:Chickens; D017931:DNA Primers; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic / Q000528:radiation effects; D016758:Genes, jun; D053616:Janus Kinase 3; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D014158:Transcription, Genetic / Q000528:radiation effects; D014407:Tumor Cells, Cultured
chemical_list: D017931:DNA Primers; D004791:Enzyme Inhibitors; D011505:Protein-Tyrosine Kinases; D053616:Janus Kinase 3