PMID- 10655230
OWN - NLM
STAT- MEDLINE
DCOM- 20000314
LR  - 20181113
IS  - 0016-6731 (Print)
IS  - 0016-6731 (Linking)
VI  - 154
IP  - 2
DP  - 2000 Feb
TI  - A mammalian homologue of GCN2 protein kinase important for translational control 
      by phosphorylation of eukaryotic initiation factor-2alpha.
PG  - 787-801
AB  - A family of protein kinases regulates translation in response to different
      cellular stresses by phosphorylation of the alpha subunit of eukaryotic
      initiation factor-2 (eIF-2alpha). In yeast, an eIF-2alpha kinase, GCN2, functions
      in translational control in response to amino acid starvation. It is thought that
      uncharged tRNA that accumulates during amino acid limitation binds to sequences
      in GCN2 homologous to histidyl-tRNA synthetase (HisRS) enzymes, leading to
      enhanced kinase catalytic activity. Given that starvation for amino acids also
      stimulates phosphorylation of eIF-2alpha in mammalian cells, we searched for and 
      identified a GCN2 homologue in mice. We cloned three different cDNAs encoding
      mouse GCN2 isoforms, derived from a single gene, that vary in their
      amino-terminal sequences. Like their yeast counterpart, the mouse GCN2 isoforms
      contain HisRS-related sequences juxtaposed to the kinase catalytic domain. While 
      GCN2 mRNA was found in all mouse tissues examined, the isoforms appear to be
      differentially expressed. Mouse GCN2 expressed in yeast was found to inhibit
      growth by hyperphosphorylation of eIF-2alpha, requiring both the kinase catalytic
      domain and the HisRS-related sequences. Additionally, lysates prepared from yeast
      expressing mGCN2 were found to phosphorylate recombinant eIF-2alpha substrate.
      Mouse GCN2 activity in both the in vivo and in vitro assays required the presence
      of serine-51, the known regulatory phosphorylation site in eIF-2alpha. Together, 
      our studies identify a new mammalian eIF-2alpha kinase, GCN2, that can mediate
      translational control.
FAU - Sood, R
AU  - Sood R
AD  - Department of Biochemistry and Molecular Biology, Indiana University School of
      Medicine, Indianapolis, Indiana 46202, USA.
FAU - Porter, A C
AU  - Porter AC
FAU - Olsen, D A
AU  - Olsen DA
FAU - Cavener, D R
AU  - Cavener DR
FAU - Wek, R C
AU  - Wek RC
LA  - eng
GR  - GM49164/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Genetics
JT  - Genetics
JID - 0374636
RN  - 0 (DNA, Complementary)
RN  - 0 (Eukaryotic Initiation Factor-2)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.1 (Eif2ak4 protein, mouse)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 6.1.1.21 (Histidine-tRNA Ligase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cloning, Molecular
MH  - DNA, Complementary
MH  - Eukaryotic Initiation Factor-2/*metabolism
MH  - Histidine-tRNA Ligase/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Phosphorylation
MH  - *Protein Biosynthesis
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein-Serine-Threonine Kinases
MH  - RNA, Messenger/genetics
MH  - Sequence Homology, Amino Acid
PMC - PMC1460965
EDAT- 2000/02/03 09:00
MHDA- 2000/03/18 09:00
CRDT- 2000/02/03 09:00
PHST- 2000/02/03 09:00 [pubmed]
PHST- 2000/03/18 09:00 [medline]
PHST- 2000/02/03 09:00 [entrez]
PST - ppublish
SO  - Genetics. 2000 Feb;154(2):787-801.