Mutations that bypass tRNA binding activate the intrinsically defective kinase domain in GCN2

Genes and Development

Volumn 16, Issue 10, 2002, Pages 1271-1280

  Qiu, Hongfang ^a   Hu, Cuihua ^a   Dong, Jinsheng ^a   Hinnebusch, Alan G ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

eIF2 Kinase; GCN2; Regulation; Translation; tRNA

Indexed keywords

AMINO ACID; HISTIDINE TRANSFER RNA LIGASE; PROTEIN KINASE; TRANSFER RNA;

ARTICLE; AUTOPHOSPHORYLATION; CONFORMATIONAL TRANSITION; ENZYME ACTIVE SITE; ENZYME ACTIVITY; IMMUNOBLOTTING; MUTATION; NONHUMAN; PHENOTYPE; POLYACRYLAMIDE GEL ELECTROPHORESIS; PRIORITY JOURNAL; RIBOSOME; RNA BINDING;

BINDING SITES; DIMERIZATION; ENZYME ACTIVATION; GENE EXPRESSION REGULATION; HISTIDINE-TRNA LIGASE; MUTAGENESIS, SITE-DIRECTED; MUTATION; PHOSPHORYLATION; PROTEIN KINASES; PROTEIN STRUCTURE, TERTIARY; RNA, TRANSFER;

EID: 0037093333     PISSN: 08909369     EISSN: None     Source Type: Journal    
DOI: 10.1101/gad.979402     Document Type: Article

References (21)

1. Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA binding domain
2. Association of GCN1/GCN20 regulatory complex with the conserved N-terminal domain of eIF2α kinase GCN2 is required for GCN2 activation in vivo
3. The eukaryotic protein kinase superfamily
4. The eukaryotic protein kinase superfamily: Kinase (catalytic) domain structure and classification
5. Regulated translation initiation controls stress-induced gene expression in mammalian cells
6. Translational control of GCN4: Genespecific regulation by phosphorylation of eIF2
7. Mechanism of CDK activation revealed by the structure of a cyclinA-CDK2 complex
8. Active and inactive protein kinases: Structural basis for regulation
9. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase
10. Positive regulatory interactions of the HIS4 gene of Saccharomyces cerevisiae
11. Evidence that GCN1 and GCN20, translational regulators of GCN4, function on enlongating ribosomes in activation of the eIF2a kinase GCN2
12. Homologous segments in three subunits of the guanine nucleotide exchange factor elF2B mediate translational regulation by phosphorylation of elF2
13. The tRNA-binding moiety in GCN2 contains a dimerization domain that interacts with the kinase domain and is required for tRNA binding and kinase activation
14. Dimerization by translation initiation factor 2 kinase GCN2 is mediated by interactions in the C-terminal ribosomebinding region and the protein kinase domain
15. Mutations activating the yeast eIF-2a kinase GCN2: Isolation of alleles altering the domain related to histidyl-tRNA synthetases
16. Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2a kinases PKR and GCN2
17. Separate domains in GCN1 for binding protein kinase GCN2 and ribosomes are required for GCN2 activation in amino acid-starved cells
18. Juxtaposition of domains homologous to protein kinases and histidyl-tRNA synthetases in GCN2 protein suggests a mechanism for coupling GCN4 expression to amino acid availability
19. Identification of positive-acting domains in GCN2 protein kinase required for translational activation of GCN4 expression
20. The histidyl-tRNA synthetase-related sequence in the eIF-2a protein kinase GCN2 interacts with tRNA and is required for activation in response to starvation for different amino acids
21. Ribosome-binding domain of eukaryotic initiation factor-2 kinase GCN2 facilitates translation control