TAILIEUCHUNG - Báo cáo Y học: Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1 Implications for apoptosis signaling pathways

Double-stranded RNA-activated protein kinase (PKR), a serine/threonine kinase, is activated in virus-infected cells and acts as an antiviral machinery of type I interferons. PKR controls several stress response pathways induced by double-stranded RNA, tumor necrosis factor-aor lipo-polysaccharide, which result in the activation of stress-acti-vated protein kinase/c-Jun NH2 -terminal kinase and p38 of the mitogen-activated protein kinase family. | Eur. J. Biochem. 269 6126-6132 2002 FEBS 2002 doi Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1 Implications for apoptosis signaling pathways Takenori Takizawa1 Chizuru Tatematsu1 and Yoshinobu Nakanishi2 1 Department of Biochemistry Institute for Developmental Research Aichi Human Service Center Kasugai Aichi Japan 2Graduate school of Medical Science Kanazawa University Kanazawa Ishikawa Japan Double-stranded RNA-activated protein kinase PKR a serine threonine kinase is activated in virus-infected cells and acts as an antiviral machinery of type I interferons. PKR controls several stress response pathways induced by double-stranded RNA tumor necrosis factor-a or lipopolysaccharide which result in the activation of stress-activated protein kinase c-Jun NH2-terminal kinase and p38 of the mitogen-activated protein kinase family. Here we showed a novel interaction between PKR and apoptosis signal-regulating kinase 1 ASK1 one of the members of the mitogen-activated protein kinase kinase kinase family which is activated in response to a variety of apoptosisinducing stimuli. PKR and ASK1 showed predominant cytoplasmic localization in COS-1 cells transfected with both cDNAs and coimmunoprecipitated from the cell extracts. A dominant negative mutant of PKR PKR-KR inhibited both the apoptosis and p38 activation induced by ASK1 in vivo. Consistently PKR-KR inhibited the autophosphorylation of ASK1 in vitro and exposure to poly I -poly C increased the phosphorylation of ASK1 in vivo. These results indicate the existence of a link between PKR and ASK1 which modifies downstream MAPK. Keywords ASK1 apoptosis MAPK PKR signal transduction. The interferon-inducible double-stranded RNA dsRNA -activated protein kinase PKR is a serine threonine kinase ubiquitously expressed in mammalian cells 1 2 . PKR is activated by a variety of dsRNA molecules generated during viral infection 3 . Upon its activation

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