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  Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2α (elF2α) kinase

Pomar, N., Berlanga, J. J., Campuzano, S., Hernandez, G., Elias, M., & de Haro, C. (2003). Functional characterization of Drosophila melanogaster PERK eukaryotic initiation factor 2α (elF2α) kinase. European Journal of Biochemistry, 270, 293-306.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F186-1 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0027-E418-1
Genre: Journal Article

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Pomar, N., Author
Berlanga, J. J., Author
Campuzano, S., Author
Hernandez, G.1, Author              
Elias, M., Author
de Haro, C., Author
Affiliations:
1Department of Molecular Biology, MPI for biophysical chemistry, Max Planck Society, ou_578628              

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Free keywords: elF2α kinase; Drosophila melanogaster; translational control; PERK homologue; ER stress
 Abstract: Four distinct eukaryotic initiation factor 2α (eIF2α) kinases phosphorylate eIF2a at S51 and regulate protein synthesis in response to various environmental stresses. These are the hemin-regulated inhibitor (HRI), the interferon-inducible dsRNA-dependent kinase (PKR), the endoplasmic reticulum (ER)-resident kinase (PERK) and the GCN2 protein kinase. Whereas HRI and PKR appear to be restricted to mammalian cells, GCN2 and PERK seem to be widely distributed in eukaryotes. In this study, we have characterized the second eIF2α kinase found in Drosophila, a PERK homologue (DPERK). Expression of DPERK is developmentally regulated. During embryogenesis, DPERK expression becomes concentrated in the endodermal cells of the gut and in the germline precursor cells. Recombinant wild-type DPERK, but not the inactive DPERK-K671R mutant, exhibited an autokinase activity, specifically phosphorylated Drosophila eIF2α at S50, and functionally replaced the endogenous Saccharomyces cerevisiae GCN2. The full length protein, when expressed in 293T cells, located in the ER-enriched fraction, and its subcellular localization changed with deletion of different N-terminal fragments. Kinase activity assays with these DPERK deletion mutants suggested that DPERK localization facilitates its in vivo function. Similar to mammalian PERK, DPERK forms oligomers in vivo and DPERK activity appears to be regulated by ER stress. Furthermore, the stable complexes between wild-type DPERK and DPERK-K671R mutant were mediated through the N terminus of the proteins and exhibited an in vitro eIF2α kinase activity.

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Language(s): eng - English
 Dates: 2003-02
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Identifiers: eDoc: 59957
 Degree: -

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Title: European Journal of Biochemistry
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 270 Sequence Number: - Start / End Page: 293 - 306 Identifier: -