ArticleMolecular biology of the cell2007
A novel function of eIF2alpha kinases as inducers of the phosphoinositide-3 kinase signaling pathway.
Article in Molecular biology of the cell, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 84 citations in OpenAlex.
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- Long non-coding RNA DARS-AS1 promotes tumor progression by directly suppressing PACT-mediated cellular stress.Communications biology · 2022Article
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- Crosstalk between endoplasmic reticulum stress and oxidative stress: a dynamic duo in multiple myeloma.Cellular and molecular life sciences : CMLS · 2021Review
- Therapeutic Targeting of Autophagy in Pancreatic Ductal Adenocarcinoma.Frontiers in pharmacology · 2021Review
- Targeting the Integrated Stress Response in Cancer Therapy.Frontiers in pharmacology · 2021Review
- Chemotherapy Resistance Explained through Endoplasmic Reticulum Stress-Dependent Signaling.Cancers · 2019Review
- Role of the ISR-ATF4 pathway and its cross talk with Nrf2 in mitochondrial quality control.Journal of clinical biochemistry and nutrition · 2019Review
- Leishmania donovani induced Unfolded Protein Response delays host cell apoptosis in PERK dependent manner.PLoS neglected tropical diseases · 2018Article
- CONCORD biomarker prediction for novel drug introduction to different cancer types.Oncotarget · 2018Article
- Mutations in THAP1/DYT6 reveal that diverse dystonia genes disrupt similar neuronal pathways and functions.PLoS genetics · 2018Article
- The eIF2-alpha kinase HRI: a potential target beyond the red blood cell.Expert opinion on therapeutic targets · 2017Review
- Transcriptional signature of lymphoblastoid cell lines ofOncotarget · 2017Article
- Polycystin-1 inhibits eIF2α phosphorylation and cell apoptosis through a PKR-eIF2α pathway.Scientific reports · 2017Article
- PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.PLoS genetics · 2016Article
- Disruption of Protein Processing in the Endoplasmic Reticulum of DYT1 Knock-in Mice Implicates Novel Pathways in Dystonia Pathogenesis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- The integrated stress response.EMBO reports · 2016Review
- Neuronal human BACE1 knockin induces systemic diabetes in mice.Diabetologia · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Phosphoinositide-3 kinase (PI3K) plays an important role in signal transduction in response to a wide range of cellular stimuli involved in cellular processes that promote cell proliferation and survival. Phosphorylation of the alpha subunit of the eukaryotic translation initiation factor eIF2 at Ser51 takes place in response to various types of environmental stress and is essential for regulation of translation initiation. Herein, we show that a conditionally active form of the eIF2alpha kinase PKR acts upstream of PI3K and turns on the Akt/PKB-FRAP/mTOR pathway leading to S6 and 4E-BP1 phosphorylation. Also, induction of PI3K signaling antagonizes the apoptotic and protein synthesis inhibitory effects of the conditionally active PKR. Furthermore, induction of the PI3K pathway is impaired in PKR(-/-) or PERK(-/-) mouse embryonic fibroblasts (MEFs) in response to various stimuli that activate each eIF2alpha kinase. Mechanistically, PI3K signaling activation is indirect and requires the inhibition of protein synthesis by eIF2alpha phosphorylation as demonstrated by the inactivation of endogenous eIF2alpha by small interfering RNA or utilization of MEFs bearing the eIF2alpha Ser51Ala mutation. Our data reveal a novel property of eIF2alpha kinases as activators of PI3K signaling and cell survival.
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