GCN2, an eIF-2a protein kinase containing sequences related to aminoacyl-trna synthetases, is conserved from yeast to mammals

R. Sood, R. C. Wek

Research output: Contribution to journalArticlepeer-review

Abstract

Phosphorylation of the a subunit of cukaryotic initiation factor-2 (eIF-2) regulates protein synthesis in response to environmental stresses. To date, the genes encoding three eIF-2a protein kinases have been cloned and characterized. Two mammalian enzymes, PKR and HR1, control translation predominantly in response to viral infection and heme deprivation, respectively. The third is the yeast kinase GCN2 which alters protein synthesis in response to amino acid starvation. GCN2 is a multidomain protein with a kinase region juxtaposed to sequences homologous to the histidyl-tRNA synthetases (HisRS). Uncharged tRNA that accumulates during amino acid starvation is thought to bind to the synthetase-related domain and stimulate GCN2 phosphorylation of eIF-2n. Several studies in mammalian systems have also shown elevated levels of eIF-2a phosphorylation in response to amino acid starvation. With this cue, we have identified a cDNA encoding the mammalian homolog of the yeast GCN2 in mouse (mGCN2). The mGCN2 contains both the kinase catalyticdomain and the HisRS-like sequences. Northern blot analysis has revealed the presence of a 5.5-kb transcript in all mouse tissues examined (heart, brain, spleen, lung, liver, skeletal muscle, kidney, testis). Interestingly, we detected a second mRNA of greater than 10 kb length which is present only in skeletal muscle suggesting another GCN2 isoform. These findings suggest that the mechanism of phosphorylation of eIF-2a in response to amino acid starvation is conserved from yeast to mammals.

Original languageEnglish (US)
Pages (from-to)A1231
JournalFASEB Journal
Volume11
Issue number9
StatePublished - Dec 1 1997

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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