PMID- 10542257
OWN - NLM
STAT- MEDLINE
DCOM- 19991213
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 45
DP  - 1999 Nov 5
TI  - The interferon-induced double-stranded RNA-activated protein kinase PKR will
      phosphorylate serine, threonine, or tyrosine at residue 51 in eukaryotic
      initiation factor 2alpha.
PG  - 32198-203
AB  - The family of eukaryotic initiation factor 2alpha (eIF2alpha) protein kinases
      plays an important role in regulating cellular protein synthesis under stress
      conditions. The mammalian kinases PKR and HRI and the yeast kinase GCN2
      specifically phosphorylate Ser-51 on the alpha subunit of the translation
      initiation factor eIF2. By using an in vivo assay in yeast, the substrate
      specificity of these three eIF2alpha kinases was examined by substituting Ser-51 
      in eIF2alpha with Thr or Tyr. In yeast, phosphorylation of eIF2 inhibits general 
      translation but derepresses translation of the GCN4 mRNA. All three kinases
      phosphorylated Thr in place of Ser-51 and were able to regulate general and
      GCN4-specific translation. In addition, both PKR and HRI were found to
      phosphorylate eIF2alpha-S51Y and stimulate GCN4 expression. Isoelectric focusing 
      analysis of eIF2alpha followed by detection using anti-eIF2alpha and
      anti-phosphotyrosine-specific antibodies demonstrated that PKR and HRI
      phosphorylated eIF2alpha-S51Y on Tyr in vivo. These results provide new insights 
      into the substrate recognition properties of the eIF2alpha kinases, and they are 
      intriguing considering the potential for alternate substrates for PKR in cellular
      signaling and growth control pathways.
FAU - Lu, J
AU  - Lu J
AD  - Laboratory of Eukaryotic Gene Regulation, NICHD, National Institutes of Health,
      Bethesda, Maryland 20892-2716, USA.
FAU - O'Hara, E B
AU  - O'Hara EB
FAU - Trieselmann, B A
AU  - Trieselmann BA
FAU - Romano, P R
AU  - Romano PR
FAU - Dever, T E
AU  - Dever TE
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 2ZD004190S (Threonine)
RN  - 42HK56048U (Tyrosine)
RN  - 452VLY9402 (Serine)
RN  - EC 2.7.11.1 (eIF-2 Kinase)
SB  - IM
MH  - Alleles
MH  - Cell Line
MH  - Eukaryotic Initiation Factor-2/chemistry/*metabolism
MH  - Humans
MH  - Isoelectric Focusing
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Serine/*metabolism
MH  - Substrate Specificity
MH  - Threonine/*metabolism
MH  - Tyrosine/*metabolism
MH  - eIF-2 Kinase/*metabolism
EDAT- 1999/11/05 00:00
MHDA- 1999/11/05 00:01
CRDT- 1999/11/05 00:00
PHST- 1999/11/05 00:00 [pubmed]
PHST- 1999/11/05 00:01 [medline]
PHST- 1999/11/05 00:00 [entrez]
AID - 10.1074/jbc.274.45.32198 [doi]
AID - S0021-9258(19)51545-9 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Nov 5;274(45):32198-203. doi: 10.1074/jbc.274.45.32198.