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Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex

J Gil1, J Alcamí, M Esteban

  • 1Department of Molecular and Cellular Biology, Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, (CSIC), Campus Universidad Autónoma, 28049 Madrid, Spain.

Oncogene
|March 21, 2000
PubMed

Insights

The double-stranded RNA-dependent protein kinase (PKR) activates the NF-kappa B pathway by interacting with the IKK complex. This mechanism is crucial for PKR

Area of Science:

  • Molecular Biology
  • Immunology
  • Virology

Background:

  • The double-stranded RNA-dependent protein kinase (PKR) is known for translational control.
  • PKR also acts as a transcriptional regulator with antiviral and antitumoural roles.
  • PKR-induced NF-kappa B activation is linked to apoptosis.

Purpose of the Study:

  • To elucidate the mechanism by which PKR mediates NF-kappa B activation upon double-stranded RNA (dsRNA) exposure.
  • To identify the specific NF-kappa B complexes and upstream signaling components involved.

Main Methods:

  • Utilized vaccinia virus (VV) recombinants expressing PKR.
  • Induced endogenous PKR with poly I:C (pIC) treatment.
  • Employed gel shift assays, luciferase reporter assays, and immunoprecipitation.

Main Results:

  • PKR-induced NF-kappa B complexes primarily consist of p50-p65 and c-rel-p50 heterodimers.
  • PKR phosphorylates I kappa B alpha at serine 32, leading to its degradation.
  • PKR interacts with the IKK complex (IKK1/IKK2), and dominant-negative mutants inhibit NF-kappa B activation.

Conclusions:

  • PKR activates the NF-kappa B pathway through the I kappa B kinase (IKK) complex.
  • This activation mechanism is a key physiological function of PKR.
  • Understanding this pathway is vital for antiviral and antitumoural strategies.

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