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Studying RNA Interactors of Protein Kinase RNA-Activated during the Mammalian Cell Cycle
10:05

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Double-stranded RNA-activated protein kinase interacts with apoptosis signal-regulating kinase 1. Implications for

Takenori Takizawa1, Chizuru Tatematsu, Yoshinobu Nakanishi

  • 1Department of Biochemistry, Institute for Developmental Research, Aichi Human Service Center, Kasugai, Aichi, Japan. takizawa@inst-hsc.pref.aichi.jp

European Journal of Biochemistry
|December 11, 2002
PubMed

Insights

Double-stranded RNA-activated protein kinase (PKR) interacts with apoptosis signal-regulating kinase 1 (ASK1), revealing a new link in cellular stress and apoptosis pathways. This interaction influences downstream mitogen-activated protein kinase (MAPK) signaling.

Area of Science:

  • Molecular Biology
  • Cellular Signaling
  • Virology

Background:

  • Double-stranded RNA-activated protein kinase (PKR) is a key antiviral effector in the type I interferon response.
  • PKR regulates stress pathways involving tumor necrosis factor-alpha and lipopolysaccharide, activating stress-activated protein kinase/c-Jun NH2-terminal kinase and p38.
  • Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase kinase kinase activated by apoptosis-inducing stimuli.

Purpose of the Study:

  • To investigate a potential novel interaction between PKR and ASK1.
  • To elucidate the functional consequences of the PKR-ASK1 interaction on cellular signaling pathways.

Main Methods:

  • Co-immunoprecipitation assays to detect PKR-ASK1 interaction in transfected COS-1 cells.
  • In vitro kinase assays using a dominant-negative PKR mutant (PKR-KR).
  • In vivo studies assessing apoptosis and p38 activation, and ASK1 phosphorylation upon poly(I)-poly(C) exposure.

Main Results:

  • PKR and ASK1 were found to co-localize in the cytoplasm and co-immunoprecipitate.
  • A dominant-negative PKR mutant inhibited ASK1-induced apoptosis and p38 activation in vivo.
  • PKR-KR inhibited ASK1 autophosphorylation in vitro, and poly(I)-poly(C) treatment enhanced ASK1 phosphorylation in vivo.

Conclusions:

  • A novel functional link exists between PKR and ASK1.
  • This interaction modulates downstream mitogen-activated protein kinase (MAPK) signaling pathways.
  • The findings provide new insights into cellular stress responses and apoptosis regulation.

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