Ribosome targeting of eIF-2 protein kinases, GCN2 and PKR

S. Zhu, A. Sobolov, R. C. Wek

Research output: Contribution to journalArticle


A family of protein kinases regulate translation by phosphorylation of eukaryotic initiation factor 2 (eIF-2). One family member from yeast, GCN2, is a multidomain protein that contains both a kinase catalytic region as well as a sequences homologous to histidyl-tRNA synthetases. It is thought that uncharged tRNAs accumulating during amino acid starvation interact with the synthetase-related domain and activate GCN2 phosphorylation of eIF-2. Previous work suggested that the extreme carboxyl terminal region of GCN2 was involved in ribosome targeting. In this report, we observed that this region of GCN2 contains a lysine-rich sequence with features similar to the double-stranded-RNA (dsRNA) binding motif found in the related eIF-2 kinase, PKR. Regulation of PKR is also thought to involve association with ribosomes. Mutations in the conserved lysine residues abolished GCN2 association with ribosomes, as well as GCN2 regulatory function in vivo. The carboxyl terminus of GCN2 is sufficient for association for ribosomes, since recombinant protein containing this portion of the kinase is associated with ribosomes when added to cellular extracts. This in vitro association with ribosomes was also abolished by mutations in the lysine residues. Given the role of the dsRNA-binding motiflike sequence in GCN2 ribosome association, we propose that one of the functions of dsRNA-binding motifs is to target proteins to ribosomes. Experiments analyzing mutant versions of PKR containing deletions of the dsRNA-binding motifs support this model. Ribosomal targeting may be important for regulating proteins involved in translation control by providing these proteins access to enzymatic substrates or regulatory ligands.

Original languageEnglish (US)
Pages (from-to)A1267
JournalFASEB Journal
Issue number6
StatePublished - Dec 1 1996

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'Ribosome targeting of eIF-2 protein kinases, GCN2 and PKR'. Together they form a unique fingerprint.

  • Cite this