ReviewCellular and molecular life sciences : CMLS2013
The eIF2α kinases: their structures and functions.
Review in Cellular and molecular life sciences : CMLS, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 531 papers.
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Who cites it
531 citing papers in PubMed, 831 citations in OpenAlex.
- Investigational eIF2B activator DNL343 modulates the integrated stress response in preclinical models of TDP-43 pathology and individuals with ALS in a randomized clinical trial.Nature communications · 2025Trial
- Tramadol induced hypoxia signaling and paraptosis-like cell death in breast cancer cells via HIF-1α and ATF4 dependent pathways.Redox report : communications in free radical research · 2026Article
- The Effects of Extracellular Vesicles From Cancer Cells in Acidosis or ER Stress to Endothelial Cells: Angiogenesis and Endothelial Activation.Biology of the cell · 2026Article
- Tuning intracellular immunity by Nodamura virus B2 protein enhances self-amplifying RNA activity.Nature communications · 2026Article
- From Cellular Stress to Systemic Adaptation: The Circadian Clock and Stress Response at Cellular and Systemic Levels.International journal of molecular sciences · 2026Review
- Article
- Cepharanthine inhibits tick‑borne encephalitis virus infection through modulation of the stress and inflammation response.International journal of molecular medicine · 2026Article
- Conditional eIF2A Deletion Suggests Extra-Adipose Mechanisms Underlying Metabolic Syndrome in Total-Body eIF2A Knockout Mice.FASEB bioAdvances · 2026Article
- Microbiome-derived metabolites shape CD4+ T cell differentiation and immune aging in HIV-1 infection.JCI insight · 2026Article
- Systematic comparison of temporal hepatotoxicant-induced gene network responses across 3 liver test systems.Toxicological sciences : an official journal of the Society of Toxicology · 2026Article
- Non-canonical signaling hubs upon inhibition of MyD88-ERK interaction in cancer.Cell death & disease · 2026Article
- Global cellular responses to lysosomal damage.Current biology : CB · 2026Review
- Kinetic control of macrophage death by PTM-turnover crosstalk in infection and inflammation.Cell chemical biology · 2026Review
- Cellular Responses to Flavivirus Infections: Stress Signaling at the Crossroads of Host Defense and Virus Infection.Viruses · 2026Review
- The unfolded protein response and its activation by insulin in muscle are not altered by obesity or type 2 diabetes.Clinical science (London, England : 1979) · 2026Article
- Genomic insights into the tunicamycin-induced endoplasmic reticulum stress response in peripheral blood mononuclear cells: A comprehensive RNA sequencing analysis.Biochemistry and biophysics reports · 2026Article
- Targeting endoplasmic reticulum stress and protein misfolding in schizophrenia: the emerging promise of sigma-1 receptor agonists.Psychopharmacology · 2026Review
- PKR condensation at viral replication complexes initiates its activation.Cell reports · 2026Article
- Unfolding Resilience: Molecular Integration of the Integrated Stress Response and Mitochondrial UPR in Skeletal Muscle Homeostasis.Muscles (Basel, Switzerland) · 2026Review
- A molecular stabiliser of an inhibitory eIF2B-eIF2(αP) complex activates the Integrated Stress Response.Nature communications · 2026Article
471 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cell signaling in response to an array of diverse stress stimuli converges on the phosphorylation of the α-subunit of eukaryotic initiation factor 2 (eIF2). Phosphorylation of eIF2α on serine 51 results in a severe decline in de novo protein synthesis and is an important strategy in the cell's armory against stressful insults including viral infection, the accumulation of misfolded proteins, and starvation. The phosphorylation of eIF2α is carried out by a family of four kinases, PERK (PKR-like ER kinase), PKR (protein kinase double-stranded RNA-dependent), GCN2 (general control non-derepressible-2), and HRI (heme-regulated inhibitor). Each primarily responds to a distinct type of stress or stresses. Thus, while significant sequence similarity exists between the eIF2α kinases in their kinase domains, underlying their common role in phosphorylating eIF2α, additional unique features determine the regulation of these four proteins, that is, what signals activate them. This review will describe the structure of each eIF2α kinase and discuss how this is linked to their activation and function. In parallel to the general translational attenuation elicited by eIF2α kinase activation the translation of stress-induced mRNAs, most notably activating transcription factor 4 (ATF4) is enhanced and these set in motion cascades of gene expression constituting the integrated stress response (ISR), which seek to remediate stress and restore homeostasis. Depending on the cellular context and concurrent signaling pathways active, however, translational attenuation can also facilitate apoptosis. Accordingly, the role of the kinases in determining cell fate will also be discussed.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.