title: Development of transgenic mice expressing a conditionally active form of the eIF2α kinase PKR.
abstract: Phosphorylation of the alpha (α) subunit of the eukaryotic initiation factor 2 (eIF2) at serine 51 is an important mechanism of translational control in response to various forms of environmental stress. In metazoans, eIF2α phosphorylation is mediated by four kinases each of which becomes activated by distinct stimuli. Previous work established that expression of a chimera protein comprising of the bacteria Gyrase B N-terminal (GyrB) domain fused to the kinase domain (KD) of the eIF2α kinase PKR is capable of inducing eIF2α phosphorylation in cultured cells after treatment with the antibiotic coumermycin. Herein, we report the development of transgenic mice expressing the fusion protein GyrB.PKR ubiquitously. Treatment of mice with coumermycin induces eIF2α phosphorylation in vivo as demonstrated by immunoblotting and immunoshistochemistry of mouse tissues. The GyrB.PKR transgene represents a useful model system to investigate the biological effects of the conditional induction of eIF2α phosphorylation in vivo in the absence of parallel signaling pathways that are elicited in response to stress.
authors: Lady Davis Institute for Medical Research, McGill University, Sir Mortimer B. Davis-Jewish General Hospital, Montreal, Quebec H3T 1E2, Canada. andreas.papadakis@mail.mcgill.ca
authors: Andreas I
authors: AI
authors: Papadakis
authors: Dionissios
authors: D
authors: Baltzis
authors: Ryan C
authors: RC
authors: Buensuceso
authors: Philippos
authors: P
authors: Peidis
authors: Antonis E
authors: AE
authors: Koromilas
mesh_terms: D049933:Aminocoumarins / Q000494:pharmacology; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D027081:DNA Gyrase / Q000235:genetics / Q000378:metabolism*; D015852:Eukaryotic Initiation Factor-2 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D005838:Genotype; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D010766:Phosphorylation / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013312:Stress, Physiological; D059005:Topoisomerase II Inhibitors; D019076:Transgenes / Q000235:genetics; D019892:eIF-2 Kinase / Q000235:genetics / Q000378:metabolism*
chemical_list: D049933:Aminocoumarins; D001426:Bacterial Proteins; D015852:Eukaryotic Initiation Factor-2; D011993:Recombinant Fusion Proteins; D059005:Topoisomerase II Inhibitors; D019892:eIF-2 Kinase; D027081:DNA Gyrase; C004628:coumermycin