Reference: Cardin E, et al. (2007) Nck-1 selectively modulates eIF2alphaSer51 phosphorylation by a subset of eIF2alpha-kinases. FEBS J 274(22):5865-75

Reference Help

Abstract


Phosphorylation of the alpha-subunit of the eukaryotic initiation factor 2 (eIF2) on Ser51 is an early event associated with the down-regulation of protein synthesis at the level of translation and initiation of a transcriptional program. This constitutes a potent mechanism to overcome various stress conditions. In mammals, four eIF2alpha-kinases [PKR-like endoplasmic reticulum kinase (PERK), dsRNA-activated protein kinase (PKR), heme regulated inhibitor (HRI) and general control nonderepressible-2 (GCN2)], activated following specific stresses, have been shown to be involved in this process. In this article, we report that the ubiquitously expressed adaptor protein Nck, composed only of Src homology domains and classically implicated in cell signaling by activated plasma membrane receptor tyrosine kinases, modulates eIF2alpha-kinase-mediated eIF2alphaSer51 phosphorylation in a specific manner. Our results show that Nck not only prevents eIF2alpha phosphorylation upon PERK activation, as reported previously, but also reduces eIF2alpha phosphorylation in conditions leading to PKR and HRI activation. By contrast, the overexpression of Nck in mammalian cells fails to attenuate eIF2alphaSer51 phosphorylation in response to amino acid starvation, a stress well known to activate GCN2. This observation is further confirmed by showing that Nck fails to alter eIF2alphaSer51 phosphorylation in Saccharomyces cerevisiae, for which the sole eIF2alpha-kinase is Gcn2p. Our results suggest the existence of a novel mechanism that specifically modulates the phosphorylation of eIF2alpha on Ser51 under various stress conditions.

Reference Type
Journal Article | Research Support, Non-U.S. Gov't
Authors
Cardin E, Latreille M, Khoury C, Greenwood MT, Larose L
Primary Lit For
Additional Lit For
Review For

Gene Ontology Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene/Complex Qualifier Gene Ontology Term Aspect Annotation Extension Evidence Method Source Assigned On Reference

Phenotype Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details.

Gene Phenotype Experiment Type Mutant Information Strain Background Chemical Details Reference

Disease Annotations


Increase the total number of rows showing on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Disease Ontology Term Qualifier Evidence Method Source Assigned On Reference

Regulation Annotations


Increase the total number of rows displayed on this page using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; to filter the table by a specific experiment type, type a keyword into the Filter box (for example, “microarray”); download this table as a .txt file using the Download button or click Analyze to further view and analyze the list of target genes using GO Term Finder, GO Slim Mapper, or SPELL.

Regulator Target Direction Regulation Of Happens During Method Evidence

Post-translational Modifications


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Site Modification Modifier Reference

Interaction Annotations


Genetic Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Allele Assay Annotation Action Phenotype SGA score P-value Source Reference

Physical Interactions

Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through the table's pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table; click on the small "i" buttons located within a cell for an annotation to view further details about experiment type and any other genes involved in the interaction.

Interactor Interactor Assay Annotation Action Modification Source Reference

Functional Complementation Annotations


Increase the total number of rows showing on this page by using the pull-down located below the table, or use the page scroll at the table's top right to browse through its pages; use the arrows to the right of a column header to sort by that column; filter the table using the "Filter" box at the top of the table.

Gene Species Gene ID Strain background Direction Details Source Reference