PMID- 10336432
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 22
DP  - 1999 May 28
TI  - RAX, a cellular activator for double-stranded RNA-dependent protein kinase during
      stress signaling.
PG  - 15427-32
AB  - The double-stranded (ds) RNA-dependent protein kinase (PKR) regulates protein
      synthesis by phosphorylating the alpha 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.
FAU - Ito, T
AU  - Ito T
AD  - Sealy Center for Oncology and Hematology, Department of Internal Medicine, The
      University of Texas Medical Branch at Galveston, Galveston Texas 77555-1048, USA.
      tito@utmb.edu
FAU - Yang, M
AU  - Yang M
FAU - May, W S
AU  - May WS
LA  - eng
SI  - GENBANK/AF083032
SI  - GENBANK/AF083033
GR  - CA44649/CA/NCI NIH HHS/United States
GR  - HL54083/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Carrier Proteins)
RN  - 0 (Interleukin-3)
RN  - 0 (Prkra protein, mouse)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Double-Stranded)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA-Binding Proteins)
RN  - 17885-08-4 (Phosphoserine)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Carrier Proteins/chemistry/genetics
MH  - Cell Line
MH  - Enzyme Activation
MH  - Gene Expression Regulation
MH  - Interleukin-3/metabolism
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphoserine/metabolism
MH  - Protein Binding
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA, Double-Stranded/genetics
MH  - RNA, Messenger/metabolism
MH  - RNA-Binding Proteins/chemistry/*genetics
MH  - Signal Transduction/genetics
MH  - eIF-2 Kinase/*metabolism
EDAT- 1999/05/21 00:00
MHDA- 1999/05/21 00:01
CRDT- 1999/05/21 00:00
PHST- 1999/05/21 00:00 [pubmed]
PHST- 1999/05/21 00:01 [medline]
PHST- 1999/05/21 00:00 [entrez]
AID - 10.1074/jbc.274.22.15427 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 May 28;274(22):15427-32. doi: 10.1074/jbc.274.22.15427.