Linked Life Data

8099443

Source:http://linkedlifedata.com/resource/pubmed/id/8099443

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
1993-7-2
pubmed:abstractText
Phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha) in Saccharomyces cerevisiae by the GCN2 protein kinase stimulates the translation of GCN4 mRNA. The protein kinases heme-regulated inhibitor of translation (HRI) and double-stranded RNA-dependent eIF-2 alpha protein kinase (dsRNA-PK) inhibit initiation of translation in mammalian cells by phosphorylating Ser-51 of eIF-2 alpha. We show that HRI and dsRNA-PK phosphorylate yeast eIF-2 alpha in vitro and in vivo and functionally substitute for GCN2 protein to stimulate GCN4 translation in yeast. In addition, high-level expression of either mammalian kinase in yeast decreases the growth rate, a finding analogous to the inhibition of total protein synthesis by these kinases in mammalian cells. Phosphorylation of eIF-2 alpha inhibits initiation in mammalian cells by sequestering eIF-2B, the factor required for exchange of GTP for GDP on eIF-2. Mutations in the GCN3 gene, encoding a subunit of the yeast eIF-2B complex, eliminate the effects of HRI and dsRNA-PK on global and GCN4-specific translation in yeast. These results provide further in vivo evidence that phosphorylation of eIF-2 alpha inhibits translation by impairing eIF-2B function and identify GCN3 as a regulatory subunit of eIF-2B. These results also suggest that GCN4 translational control will be a good model system to study how mammalian eIF-2 alpha kinases are modulated by environmental signals and viral regulatory factors.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1348691, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1382315, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1385552, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1448107, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1671169, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1672093, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1679235, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1695551, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1718419, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1739968, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1883206, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-1955461, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-2038327, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-2249755, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-2659436, http://linkedlifedata.com/resource/pubmed/commentcorrection/8099443-3402451
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0027-8424
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
90
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4616-20
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Mammalian eukaryotic initiation factor 2 alpha kinases functionally substitute for GCN2 protein kinase in the GCN4 translational control mechanism of yeast.
pubmed:affiliation
Section on Molecular Genetics of Lower Eukaryotes, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.