The protein kinase PKR: a molecular clock that sequentially activates survival and death programs

EMBO J. 2004 Feb 11;23(3):564-71. doi: 10.1038/sj.emboj.7600078. Epub 2004 Jan 29.

Abstract

Cell death and survival play a key role in the immune system as well as during development. The control mechanisms that balance cell survival against cell death are not well understood. Here we report a novel strategy used by a single protein to regulate chronologically cell survival and death. The interferon-induced protein kinase PKR acts as a molecular clock by using catalysis-dependent and -independent activities to temporally induce cell survival prior to cell death. We show that the proapoptotic protein PKR surprisingly activates a survival pathway, which is mediated by NF-kappaB to delay apoptosis. Cell death is then induced by PKR through the phosphorylation of eIF-2alpha. This unique temporal control might serve as a paradigm for other kinases whose catalytic activity is not required for all of their functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology*
  • Cell Survival / physiology
  • Eukaryotic Initiation Factor-2 / metabolism
  • Mice
  • NF-kappa B / metabolism
  • NIH 3T3 Cells
  • Phosphorylation
  • Signal Transduction / physiology*
  • eIF-2 Kinase / metabolism*

Substances

  • Eukaryotic Initiation Factor-2
  • NF-kappa B
  • eIF-2 Kinase