EIF2AK2 Antibody

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Description

Applications and Validations

The antibody is versatile across multiple experimental platforms, as summarized below:

Tested Applications

MethodDilutionSamples
Western Blot (WB)1:5000–1:50,000A549, Jurkat, HepG2, HeLa, SH-SY5Y
Immunoprecipitation (IP)0.5–4.0 µg/mg lysateHeLa cells
IHC1:50–1:500Human kidney, testis (TE buffer pH 9.0)
IF/ICC1:50–1:500HeLa cells
ELISAN/A (validated)-

Published Applications

  • WB: 41 publications (e.g., tumor suppressor studies in breast, lung cancers) .

  • IHC: 2 publications (e.g., pancreatic cancer biomarker analysis) .

  • IP/RIP: 2+ publications (e.g., PKR activation mechanisms) .

EIF2AK2 Function and Pathways

EIF2AK2 is a serine/threonine kinase activated by:

  • Double-stranded RNA (dsRNA) during viral infections .

  • Manganese ions and heparin for non-viral stress responses .

Key Pathways

  1. Antiviral Defense: Phosphorylates eIF2α (Ser51), inhibiting global protein synthesis while upregulating stress-response genes (e.g., ATF4) .

  2. Tumor Suppression: Linked to poor prognosis in cancers (breast, lung, colorectal) when suppressed .

  3. Inflammation: Activates NF-κB and p38 MAPK pathways via interactions with TRAF and MAP2K6 .

Research Findings in Pancreatic Cancer

A 2023 study identified EIF2AK2 as a potential diagnostic and prognostic biomarker for pancreatic cancer :

  • Expression: Significantly higher in pancreatic cancer tissues vs. adjacent tissues.

  • Survival Analysis: High EIF2AK2 levels correlated with improved survival outcomes (Kaplan-Meier, Cox regression) .

  • Mechanism: Knockdown experiments in PANC-1 cells reduced proliferation and induced apoptosis (CCK-8, wound healing assays) .

Therapeutic Implications

EIF2AK2’s dual role in stress response and oncology highlights its therapeutic potential:

  • Antiviral Strategies: Targeting viral evasion mechanisms (e.g., influenza NS1 protein inhibition) .

  • Cancer Therapy: Modulating EIF2AK2 activity to enhance tumor suppression or immunotherapy efficacy .

Disease Associations

EIF2AK2 is implicated in:

  • Neurodegenerative Diseases: Alzheimer’s, Huntington’s, ALS .

  • Genetic Disorders: Dystonia 33, Leukoencephalopathy .

Citations and References

  1. Thermofisher Scientific .

  2. PMC study on pancreatic cancer .

  3. Proteintech product specifications .

  4. GeneCards database .

Product Specs

Buffer
Preservative: 0.03% Proclin 300
Constituents: 50% Glycerol, 0.01M PBS, pH 7.4
Form
Liquid
Lead Time
Typically, we can ship products within 1-3 business days of receiving your order. Delivery time may vary depending on the purchase method or location. Please consult your local distributor for specific delivery timeframes.
Synonyms
Double stranded RNA activated protein kinase antibody; E2AK2_HUMAN antibody; eIF-2A protein kinase 2 antibody; EIF2AK1 antibody; EIF2AK2 antibody; Eukaryotic translation initiation factor 2 alpha kinase 2 antibody; Eukaryotic translation initiation factor 2-alpha kinase 2 antibody; HGNC:9437 antibody; Interferon induced double stranded RNA activated protein kinase antibody; Interferon inducible elF2 alpha kinase antibody; Interferon inducible RNA dependent protein kinase antibody; Interferon-induced; double-stranded RNA-activated protein kinase antibody; Interferon-inducible RNA-dependent protein kinase antibody; MGC126524 antibody; P1/eIF-2A protein kinase antibody; P1/eIF2A protein kinase antibody; p68 kinase antibody; PKR antibody; PPP1R83 antibody; PRKR antibody; Protein kinase interferon inducible double stranded RNA dependent antibody; Protein kinase RNA activated antibody; Protein kinase RNA-activated antibody; Protein phosphatase 1 regulatory subunit 83 antibody; Serine/threonine protein kinase TIK antibody; Tyrosine protein kinase EIF2AK2 antibody
Target Names
Uniprot No.

Target Background

Function
EIF2AK2, also known as PKR, is an interferon-induced dsRNA-dependent serine/threonine-protein kinase. It plays a critical role in the innate immune response to viral infection by phosphorylating the alpha subunit of eukaryotic translation initiation factor 2 (EIF2S1/eIF-2-alpha). This phosphorylation event inhibits viral replication through the integrated stress response (ISR). The ISR mechanism involves the conversion of EIF2S1/eIF-2-alpha into a global protein synthesis inhibitor, effectively halting both cellular and viral protein synthesis. Simultaneously, the ISR initiates the preferential translation of ISR-specific mRNAs, such as the transcriptional activator ATF4.

PKR exhibits antiviral activity against a wide range of DNA and RNA viruses, including hepatitis C virus (HCV), hepatitis B virus (HBV), measles virus (MV), and herpes simplex virus 1 (HHV-1). Beyond its antiviral role, PKR also participates in the regulation of signal transduction, apoptosis, cell proliferation, and differentiation. It phosphorylates various substrates, including p53/TP53, PPP2R5A, DHX9, ILF3, IRS1, and the HHV-1 viral protein US11.

In addition to its serine/threonine-protein kinase activity, PKR also exhibits tyrosine-protein kinase activity. Upon DNA damage, it phosphorylates CDK1 at 'Tyr-4', facilitating its ubiquitination and proteasomal degradation. PKR, either as an adapter protein or through its kinase activity, can regulate diverse signaling pathways (p38 MAP kinase, NF-kappa-B, and insulin signaling pathways) and transcription factors (JUN, STAT1, STAT3, IRF1, ATF3) involved in the expression of genes encoding proinflammatory cytokines and IFNs.

PKR activates the NF-kappa-B pathway by interacting with IKBKB and TRAF family proteins. It also activates the p38 MAP kinase pathway via interaction with MAP2K6. Interestingly, PKR can act as both a positive and negative regulator of the insulin signaling pathway (ISP). It negatively regulates ISP by inducing inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) at 'Ser-312'. Conversely, it positively regulates ISP through phosphorylation of PPP2R5A, which activates FOXO1, leading to upregulation of insulin receptor substrate 2 (IRS2) expression. PKR also plays a role in regulating the assembly of the NLRP3 inflammasome and the activation of NLRP3, NLRP1, AIM2, and NLRC4 inflammasomes.

Finally, PKR contributes to the regulation of the cytoskeleton by binding to gelsolin (GSN). This interaction sequesters GSN in an inactive conformation away from actin.
Gene References Into Functions
  1. We demonstrated the activation of the PKR pathway in CADASIL. PMID: 30073405
  2. These results establish that PKR regulation through stress-induced TRBP phosphorylation is a crucial mechanism ensuring cellular recovery and preventing apoptosis due to sustained PKR activation. PMID: 29348664
  3. Auto-phosphorylation represses PKR activity. PMID: 28281686
  4. The finding that zebularine upregulates CYP gene expression through DNMT1 and PKR modulation sheds light on the mechanisms controlling hepatocyte function. This may aid in the development of new in-vitro systems utilizing high-functioning hepatocytes. PMID: 28112215
  5. Multiple studies have identified PKR as a crucial component of the host defense mechanism against viruses. The dynamic nature of PKR's structure allows it to interact with viral and cellular molecules, ultimately affecting the function of target molecules and downstream components of their pathways. [review] PMID: 29716441
  6. High PKR expression is associated with Colorectal Cancer Cell Invasiveness. PMID: 30275201
  7. The data demonstrate that E3 promotes F1 expression by blocking the activation of the double-stranded RNA-activated protein kinase R (PKR). PMID: 29997208
  8. Findings indicate that MSI1 plays a leading role in stress granule formation, which grants cancer stem cell properties and chemoresistant stress granules in GBM, in response to stressful conditions via the PKR/eIF2alpha signaling cascade. PMID: 29486283
  9. Here, the authors report that LRP16 selectively interacts and activates double-stranded RNA-dependent kinase (PKR), and also acts as scaffolds to assist the formation of a ternary complex of PKR and IKKbeta. This interaction prolongs the polymers of ADP-ribose (PAR)-dependent nuclear factor kappa B (NF-kappaB) transactivation caused by DNA-damaging agents and confers acquired chemoresistance. PMID: 28820388
  10. These data suggest that even a modest increase in expression of this weak PKR antagonist is sufficient to enable RhCMV replication in human cells. PMID: 29263260
  11. Activation of PKR by TNF-alpha mRNA element enables PKR phosphorylation. PKR phosphorylation on Ser51 is necessary and sufficient for efficient splicing of TNF-alpha mRNA. PMID: 28683312
  12. PKR is co-opted by EV-A71 via viral protease 3C-mediated proteolytic activation to facilitate viral replication. PMID: 28702377
  13. Findings suggest a novel role for PKR in lung cancer cells as a mediator of radiation resistance, possibly through translocation of the protein product to the nucleus. PMID: 27203671
  14. A novel, positive role for PKR activation and eIF2alpha phosphorylation in human globin mRNA splicing is reported. PMID: 28374749
  15. Clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9-mediated ablation of double-stranded RNA (dsRNA)-activated protein kinase R (PKR) restored p53 responses while boosting hepatitis C virus replication, showing that p53 inhibition results directly from viral activation of PKR. PMID: 28442604
  16. Gene silencing studies showed that the suppression of immunoproteasome induction is essentially dependent on protein kinase R (PKR). Indeed, the generation of a strictly immunoproteasome-dependent cytotoxic T lymphocyte epitope was impaired in in vitro processing experiments using isolated 20S proteasomes from HCV-infected cells and was restored by silencing of PKR expression. PMID: 27833096
  17. Data provide the first evidence that KSHV ORF57 plays a role in modulating the PKR/eIF2alpha/SG axis and enhances virus production during virus lytic infection. PMID: 29084250
  18. PKR is a key constituent of the metaflammasome and interacts directly with several inflammatory kinases, such as inhibitor kappaB (IkappaB) kinase (IKK) and c-Jun N-terminal kinase (JNK), insulin receptor substrate 1 (IRS1), and components of the translational machinery, such as eIF2alpha. PMID: 26831644
  19. Infection with New World arenaviruses JUNV and MACV, but not OW LASV, activated PKR, concomitant with elevated phosphorylation of the translation initiation factor alpha subunit of eukaryotic initiation factor 2. PMID: 28794024
  20. The stem-loop of noncoding RNA 886 is a structural feature critical for inhibiting PKR autophosphorylation, as well as the phosphorylation of its cellular substrate, EIF-2alpha. PMID: 28069888
  21. Protein kinase R (PKR) was required for the induction of stress granules (SGs) by mumps virus (MuV) infection and regulated type III IFN (IFN-lambda1) mRNA stability. PMID: 27560627
  22. Data establish a model in which the Influenza A virus NS1 N-terminal domain engages in a binding interaction to inhibit activation of PKR and ensure efficient viral propagation and virulence. PMID: 28250123
  23. It was established in this report that interactions between PACT, ADAR1, and HIV-1-encoded Tat protein diminish the activation of PKR in response to HIV-1 infection. PMID: 28167698
  24. In insulitic islets from living patients with recent-onset T1D, most of the overexpressed ISGs, including GBP1, TLR3, OAS1, EIF2AK2, HLA-E, IFI6, and STAT1, showed higher expression in the islet core compared with the peri-islet area containing the surrounding immune cells. PMID: 27422384
  25. NF90 exerts its antiviral activity by antagonizing the inhibitory role of NS1 on PKR phosphorylation. PMID: 27423063
  26. Crucially, Chlamydia trachomatis infection resulted in robust IRE1alpha RNAse activity that was dependent on TLR4 signaling. Inhibition of IRE1alpha RNAse activity prevented PKR activation. PMID: 27021640
  27. The expression of a Tat construct containing mutations in the basic region (49-57aa), which is responsible for the interaction with PKR, favored neither parasite growth nor IL-10 expression in infected macrophages. PMID: 26608746
  28. This study provides insight into the molecular pathology of Cornelia de Lange syndrome by establishing a relationship between NIPBL and HDAC8 mutations and PKR activation. PMID: 26725122
  29. The Newcastle disease virus-induced translation shutoff at late infection times was attributed to sustaining phosphorylation of eIF2a, which is mediated by continual activation of PKR and degradation of PP1. PMID: 26869028
  30. The sole essential function of cytomegalovirus TRS1 is to antagonize host PKR. PMID: 26716879
  31. Results show that ceramide acts at two distinct levels of the insulin signaling pathway (IRS1 and Akt). PKR, which is induced by both inflammation signals and ceramide, could play a major role in the development of insulin resistance in muscle cells. PMID: 26698173
  32. Classical swine fever virus (CSFV) infection increased the phosphorylation of eukaryotic translation initiation factor (eIF)2alpha and its kinase PKR. The activation of PKR during CSFV infection is beneficial to the virus. PMID: 25899421
  33. These data indicate a pivotal role for PKR's protein-binding function on the proliferation of pancreatic beta cells through TRAF2/RIP1/NF-kappaB/c-Myc pathways. PMID: 25715336
  34. The results from this study indicate an important role of RAX/PKR association in regulating PKR activity, as well as ethanol neurotoxicity. PMID: 25592072
  35. The G3BP1-Caprin1-PKR complex represents a new mode of PKR activation and is important for antiviral activity of G3BP1 and PKR during infection with mengovirus. PMID: 25784705
  36. The data support a model in which activating RNAs induce formation of a back-to-back parallel PKR kinase dimer, whereas nonactivating RNAs either fail to induce dimerization or produce an alternative, inactive dimer configuration. PMID: 26488609
  37. Tyrosine phosphorylated EIF2AK2 plays a role in the regulation of insulin-induced protein synthesis and in maintaining insulin sensitivity. PMID: 26321373
  38. PKR expression correlates with inferior survival and shorter remission duration for acute myeloid leukemia patients. PMID: 26202421
  39. No significant association was determined between the rs2254958 EIF2AK2 polymorphism and the development of IBD, or clinical outcome. PMID: 25607115
  40. The affinity of PACT-PACT and PACT-PKR interactions is enhanced in dystonia patient lymphoblasts, thereby leading to intensified PKR activation and enhanced cellular death. PMID: 26231208
  41. Protein levels of PRKR were significantly increased in the prefrontal cortex in chronic excessive alcohol use. PMID: 25704249
  42. The mechanism by which PK2 inhibits the model eIF2alpha kinase human RNA-dependent protein kinase (PKR), as well as native insect eIF2alpha kinases, is reported. PMID: 26216977
  43. G3BP1, G3BP2, and CAPRIN1 are required for translation of interferon-stimulated mRNAs and are targeted by a dengue virus non-coding RNA. PMID: 24992036
  44. This study demonstrates that two interferon-stimulated genes, i.e., PKR and ADAR1, have opposite effects on HTLV replication in vivo. PMID: 25389016
  45. PKR directly interacts with HIV-1 Tat and phosphorylates the first exon of Tat exclusively at five Ser/Thr residues, which inhibits Tat-mediated provirus transcription. PMID: 25653431
  46. Authors show that the PXXP domain within G3BP1 is essential for the recruitment of PKR to stress granules, for eIF2alpha phosphorylation driven by PKR, and for nucleating stress granules of normal composition. PMID: 25520508
  47. Further studies revealed that Andes virus nucleocapsid protein inhibited PKR dimerization, a critical step required for PKR autophosphorylation to attain activity. PMID: 25410857
  48. SUMO potentiates the inhibition of protein synthesis induced by PKR in response to dsRNA. PMID: 25074923
  49. Early dsRNA induced transient activation of the cellular dsRNA sensor protein kinase R (PKR), resulting in enhanced production of interferons and cytokines in cells and mice. PMID: 25297997
  50. Cyclophilin inhibitors reduce phosphorylation of PKR and eIF2alpha during HCV infection, allowing for the translation of ISG products. PMID: 24786893

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Database Links

HGNC: 9437

OMIM: 176871

KEGG: hsa:5610

STRING: 9606.ENSP00000233057

UniGene: Hs.131431

Protein Families
Protein kinase superfamily, Ser/Thr protein kinase family, GCN2 subfamily
Subcellular Location
Cytoplasm. Nucleus. Cytoplasm, perinuclear region.
Tissue Specificity
Highly expressed in thymus, spleen and bone marrow compared to non-hematopoietic tissues such as small intestine, liver, or kidney tissues. Colocalizes with GSK3B and TAU in the Alzheimer disease (AD) brain. Elevated levels seen in breast and colon carcin

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