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J Biol Chem, Vol. 274, Issue 22, 15427-15432, May 28, 1999
From the Sealy Center for Oncology and Hematology, Department of
Internal Medicine, The University of Texas Medical Branch at Galveston,
Galveston Texas 77555-1048
The double-stranded (ds)
RNA-dependent protein kinase (PKR) regulates protein
synthesis by phosphorylating the 
subunit of eukaryotic initiation
factor-2. PKR is activated by viral induced dsRNA and thought to be
involved in the host antiviral defense mechanism. PKR is also activated
by various nonviral stresses such as growth factor deprivation,
although the mechanism is unknown. By screening a mouse cDNA
expression library, we have identified an ubiquitously expressed
PKR-associated protein, RAX. RAX has a high sequence homology to human
PACT, which activates PKR in the absence of dsRNA. Although RAX also
can directly activate PKR in vitro, overexpression of RAX
does not induce PKR activation or inhibit growth of interleukin-3
(IL-3)-dependent cells in the presence of IL-3. However,
IL-3 deprivation as well as diverse cell stress treatments including
arsenite, thapsigargin, and H2O2, which are
known to inhibit protein synthesis, induce the rapid phosphorylation of
RAX followed by RAX-PKR association and activation of PKR. Therefore,
cellular RAX may be a stress-activated, physiologic activator of PKR
that couples transmembrane stress signals and protein synthesis.
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