PMID- 10504407
OWN - NLM
STAT- MEDLINE
DCOM- 19991122
LR  - 20190620
IS  - 0014-2956 (Print)
IS  - 0014-2956 (Linking)
VI  - 265
IP  - 2
DP  - 1999 Oct
TI  - Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 
      2alpha kinase.
PG  - 754-62
AB  - In eukaryotic cells, protein synthesis is regulated in response to various
      environmental stresses by phosphorylating the alpha subunit of the eukaryotic
      initiation factor 2 (eIF2alpha). Three different eIF2alpha kinases have been
      identified in mammalian cells, the heme-regulated inhibitor (HRI), the
      interferon-inducible RNA-dependent kinase (PKR) and the endoplasmic
      reticulum-resident kinase (PERK). A fourth eIF2alpha kinase, termed GCN2, was
      previously characterized from Saccharomyces cerevisiae, Drosophila melanogaster
      and Neurospora crassa. Here we describe the cloning of a mouse GCN2 cDNA (MGCN2),
      which represents the first mammalian GCN2 homolog. MGCN2 has a conserved motif,
      N-terminal to the kinase subdomain V, and a large insert of 139 amino acids
      located between subdomains IV and V that are characteristic of the known
      eIF2alpha kinases. Furthermore, MGCN2 contains a class II aminoacyl-tRNA
      synthetase domain and a degenerate kinase segment, downstream and upstream of the
      eIF2alpha kinase domain, respectively, and both are singular features of GCN2
      protein kinases. MGCN2 mRNA is expressed as a single message of approximately 5.5
      kb in a wide range of different tissues, with the highest levels in the liver and
      the brain. Specific polyclonal anti-(MGCN2) immunoprecipitated an eIF2alpha
      kinase activity and recognized a 190 kDa phosphoprotein in Western blots from
      either mouse liver or MGCN2-transfected 293 cell extracts. Interestingly, serum
      starvation increased eIF2alpha phosphorylation in MGCN2-transfected human 293T
      cells. This finding provides evidence that GCN2 is the unique eIF2alpha kinase
      present in all eukaryotes from yeast to mammals and underscores the role of MGCN2
      kinase in translational control and its potential physiological significance.
FAU - Berlanga, J J
AU  - Berlanga JJ
AD  - Centro de Biologia Molecular 'Severo Ochoa', Consejo Superior de Investigaciones 
      Cientificas, Universidad Autonoma de Madrid, Spain.
FAU - Santoyo, J
AU  - Santoyo J
FAU - De Haro, C
AU  - De Haro C
LA  - eng
SI  - GENBANK/AJ243428
SI  - GENBANK/AJ243533
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Saccharomyces cerevisiae Proteins)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Eif2ak4 protein, mouse)
RN  - EC 2.7.11.1 (GCN2 protein, S cerevisiae)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Eukaryotic Initiation Factor-2/*metabolism
MH  - Humans
MH  - Mice
MH  - Molecular Sequence Data
MH  - Phosphorylation
MH  - Protein Biosynthesis
MH  - Protein Kinases/chemistry/*genetics
MH  - Protein-Serine-Threonine Kinases
MH  - RNA, Messenger/metabolism
MH  - Recombinant Proteins/metabolism
MH  - Saccharomyces cerevisiae Proteins
MH  - Sequence Alignment
EDAT- 1999/10/03 00:00
MHDA- 1999/10/03 00:01
CRDT- 1999/10/03 00:00
PHST- 1999/10/03 00:00 [pubmed]
PHST- 1999/10/03 00:01 [medline]
PHST- 1999/10/03 00:00 [entrez]
AID - ejb780 [pii]
AID - 10.1046/j.1432-1327.1999.00780.x [doi]
PST - ppublish
SO  - Eur J Biochem. 1999 Oct;265(2):754-62. doi: 10.1046/j.1432-1327.1999.00780.x.