title: Persistent activation of c-Jun N-terminal kinase 1 (JNK1) in gamma radiation-induced apoptosis.
abstract: The c-Jun N-terminal kinases (JNK) are activated by various stimuli, including UV light, interleukin-1, tumor necrosis factor-alpha (TNF-alpha), and CD28 costimulation. Induction of JNK by TNF-alpha, a strong apoptosis inducer, implies a possible role of JNK in the regulation of programmed cell death. Present studies show that lethal doses of gamma radiation (GR) induced JNK activities at the early phase of apoptosis in Jurkat T-cells. We demonstrate that JNK1 was activated by either the T-cell activation signals, anti-CD28 monoclonal antibody plus phorbol 12-myristate 13-acetate (PMA), or the apoptosis-inducing treatment, GR; however, the induction patterns were different. In contrast to the rapid and transient JNK1 activation caused by CD28 signaling plus PMA, GR induced a delayed and persistent JNK1 activation. This implies a distinct regulatory mechanism and specific function of JNK1 in irradiated cells. The nuclear and cytosolic JNK1 activities were simultaneously increased in the irradiated cells without an evident change in the protein levels. The abilities of GR to induce JNK1 activation and DNA fragmentation were correlated. Peripheral blood lymphocytes were more sensitive to GR than Jurkat cells in JNK1 induction. The responsiveness of JNK1 to GR suggests the involvement of JNK1 in the initiation of the apoptosis process.
authors.affiliation: Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: Y R
authors.initials: YR
authors.lastname: Chen
authors.forename: C F
authors.initials: CF
authors.lastname: Meyer
authors.forename: T H
authors.initials: TH
authors.lastname: Tan
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D002460:Cell Line; D004789:Enzyme Activation / Q000528:radiation effects; D005720:Gamma Rays; D006801:Humans; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D013601:T-Lymphocytes / Q000201:enzymology* / Q000473:pathology / Q000528:radiation effects
chemical_list: D017346:Protein Serine-Threonine Kinases