Written | 2012-03 | William L Blalock, Lucio Cocco |
IGM-CNR, Bologna, Rizzoli Orthopedic Institute,via di Barbiano, 1/10, 40136 Bologna, Italy (WLB); Cellular Signalling Laboratory, Department of Anatomical Sciences, University of Bologna, Via Irnerio, 48 I-40126 Bologna, Italy (LC) |
Identity |
Alias_names | PRKR |
protein kinase, interferon-inducible double stranded RNA dependent | |
Alias_symbol (synonym) | PKR |
EIF2AK1 | |
PPP1R83 | |
Other alias | p68 kinase |
PRKR, | |
HGNC (Hugo) | EIF2AK2 |
LocusID (NCBI) | 5610 |
Atlas_Id | 41866 |
Location | 2p22.2 [Link to chromosome band 2p22] |
Location_base_pair | Starts at 37105141 and ends at 37157047 bp from pter ( according to hg19-Feb_2009) [Mapping EIF2AK2.png] |
Local_order | HEAT repeat containing 5B (HEATR5B); coiled-coil domain containing 75 (CCDC75); Eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2); sulfotransferase family member, cytosolic, 6B, member 1 (SULT6B1); ribosomal protein L31 pseudogene 16 (RPL31P16). |
Fusion genes (updated 2017) | Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands) |
EIF2AK2 (2p22.2) / CEBPZ (2p22.2) | EIF2AK2 (2p22.2) / PRKD3 (2p22.2) | EIF2AK2 (2p22.2) / RMDN2 (2p22.2) | |
EIF2AK2 (2p22.2) / SULT6B1 (2p22.2) |
DNA/RNA |
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The stick diagram shows the splicing of the exons that compose PKR as well as confirmed and unconfirmed (suggested by cDNA libraries from the Mammalian Gene Collection (MGC) only) splicing products and the length of their resulting protein products. The coding sequence for PKR initiates in exon 3 at the 17th nucleotide. The coding sequence of PKR is 1656 base pairs; the individual exons contain the following coding nucleotides: exon 3 (1-118); exon 4 (119-240); exon 5 (241-389); exon 6 (390-516); exon 7 (517-593); exon 8 (594-687); exon 9 (688-722); exon 10 (723-785); exon 11 (786-908); exon 12 (909-1067); exon 13 (1068-1248); exon 14 (1249-1377); exon 15 (1378-1479); exon 16 (1480-1533); exon 17 (1534-1656). | |
Description | The EIF2AK2 gene spans approximately 50 kb and contains 17 exons. The coding sequence initiates in exon 3 (Kuhen et al., 1996). |
Transcription | Key Promoter Elements: TATA-less (No TATA Box). 1. KCS (Kinase Conserved Sequence): Nucleotides -67 to -81 from the transcriptional start site. Required for basal expression utilizing Sp factors. Also required in combination with the ISRE for interferon-stimulated expression (Kuhen and Samuel, 1997; Kuhen et al., 1998; Kuhen and Samuel, 1999; Ward and Samuel, 2002). 2. ISRE (Interferon-stimulated response element): Nucleotides -50 to -62 from the transcriptional start site. Required for the interferon-inducible expression of EIF2AK2. Regulated by the binding of STAT1, STAT2 and IRF9 (Kuhen and Samuel, 1997; Kuhen and Samuel, 1999; Ward and Samuel, 2002; Ward and Samuel, 2003). 3. P53RE (p53 response element): Two p53RE domains were identified flanking the ISRE. Acts to enhance EIF2AK2 expression following genotoxic stress (Yoon et al., 2009). Transcripts: |
Pseudogene | None. |
Protein |
Note | The protein product of the EIF2AK2 gene is typically referred to as PKR in the literature. |
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The primary amino acid sequence of PKR. The alternate exons to which the individual amino acids belong are indicated by shading. Translation of PKR initiates in exon 3 and terminates in exon 17. | |
Description | EIF2AK2/PKR is a 551 amino acid protein with a predicted molecular weight of 62,1 kDa (68-72 kDa in SDS-PAGE) and a predicted pI of 8,58. PKR first described as an interferon-inducible antiviral kinase which phosphorylated eIF2-alpha on Ser 51, is now best described as a general stress/inflammatory kinase which phosphorylates an increasing list of substrates which includes eIF2-alpha (Colthurst et al., 1987), p53 (Cuddihy et al., 1999), B56-alpha (Xu and Williams, 2000), cyclin dependent kinase (CDK)-1 (Yoon et al., 2010), and vinsulin receptor substrate-1 (Nakamura et al., 2010). |
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The primary protein structure for PKR. Key domains of the protein and the amino acids that compose them are shown, as are the key phosphorylation site(s) which are required for kinase activity (T451) (Romano et al., 1998; Zhang et al., 2001) or enhance kinase activity (Y101, Y162, S242, T255, T258, Y293 and T446) (Romano et al., 1998; Alisi et al., 2005; Su et al., 2006). | |
Expression | Ubiquitous. |
Localisation | Cytoplasm, nuclear, nucleolar. |
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Post-translational modification. (Taylor et al., 2001)a; (Su et al., 2006)b; (Romano et al., 1998)c; (Alisi et al., 2005)d; (Zhang et al., 2001)e; (Olsen et al., 2010)f; (Dephoure et al., 2008)g; (CST Curation Set Data available from Phosphosite Plus at http://www.phosphosite.org)h; (Christensen et al., 2010)i; (Kim et al., 2011)j; (Wagner et al., 2011)k. | |
Function | Major role The double-stranded RNA dependent kinase (PKR) was initially identified as an innate immune anti-viral protein approximately 35 years ago (Roberts et al., 1976b; Roberts et al., 1976a). Since then PKR has been linked to normal cell growth and differentiation, inflammation, cytokine signaling and apoptosis (Garcia et al., 2006). Altered PKR activity has been shown to play a role in neurodegenerative diseases (Alzheimer's, Huntington's and Parkinson's) and cancer (Peel et al., 2001; Peel and Bredesen, 2003; Onuki et al., 2004; Peel, 2004; Bando et al., 2005; Eley et al., 2009). PKR belongs to the eIF2α kinase family which also includes PKR-like endoplasmic reticulum kinase (PERK), general amino acid control of gene expression, non-derepressing 2 (GCN2) and heme-regulated kinase (HRI). Whereas the activation of PERK, GCN2 and HRI are in response to more specific stresses; PKR is activated in response to diverse stress signals (Shi et al., 1998; Berlanga et al., 1999; Williams, 1999; Chen, 2007). As the first known substrate of PKR was eIF2α, much of the research involving PKR has centered on its ability to regulate translation under varying conditions. Within the past ten years, PKR has been shown to play a significant role in signaling pathways involved in other cellular process such as cell proliferation, differentiation, metabolism, DNA repair and apoptosis (Garcia et al., 2006). Among the targets that PKR has been demonstrated to phosphorylate or directly influence the phosphorylation of are: p53, signal transducer and activators of transcription factors STAT1 and STAT3, inhibitor κB kinase (IKK)-β, inhibitor κB (IκB)-β, the B56α regulatory subunit of PP2A, and RNA helicase (Garcia et al., 2006; Sadler et al., 2009). In addition to these targets, PKR has been shown to influence signaling through the phosphatidylinositol-3 kinase (PI3K)/AKT pathway and transcription factors NF-κB, C/EBPα, C/EBPβ and ATF3. PKR also influences signaling through the MAPK signal transduction pathways. PKR activity is required for activation of p38MAPK and JNK in response to particular stresses, and signaling through these MAPKs is defective in PKR-/- cells. The PKR dependent mechanism involved in p38MAPK and JNK activation may involve the interaction of PKR with ASK1 or MKK6. Additionally, inhibition of protein synthesis may reduce the level of negative regulators of these kinases (Garcia et al., 2006). Activation eIF2α p53 NF-κB STATs PP2A CDK1 IRS-1 |
Homology | H. sapiens: (100%) P. troglodytes: (98%) C. lupus: (55%) B. taurus: (62%) M. musculus: (58%) R. norvegicus: (51%) G. gallus: (39%) D. rerio: (30%) |
Mutations |
Note | Although the 2p22-p21 locus is often rearranged in leukemia no data supports these alterations affecting EIF2AK2. A single nucleotide mutation was documented in a single pediatric T-ALL patient. The mutation occurred in the first double-stranded RNA binding domain and resulted in a protein that could not be activated by polyI:C (Murad et al., 2005). In a murine model of chronic lymphocytic leukemia (CLL), a rearrangement in one locus of EIF2AK2 results in the deletion of 550 nucleotides and the production of a truncated protein with dominant-negative activity (Abraham et al., 1998). |
Germinal | None. |
Somatic | - DNA: nt50 (A to G); Protein: aa17 (Tyr to Cys); Source: Pediatric T-ALL; Influence on pathology not determined. - DNA: nt1872 (C to G); Protein: aa439 (Leu to Val); Source: adenocarcinoma; Influence on pathology not determined. Single Nucleotide Polymorphisms |
Implicated in |
Note | |
Entity | Myelodysplastic syndromes (MDS) |
Note | The presence of phospho-T451 PKR (p-T451 PKR) is slightly elevated in the cytoplasm of bone-marrow mononuclear cells (BMMC) from low-risk/INT-1 MDS patients. In contrast, BMMCs from INT-2/high-risk MDS patients show an enhanced presence of p-T451 PKR with primarily nuclear localization (Follo et al., 2008). Inhibition of PKR kinase activity or expression reverses the suppressive effects of IFNγ and TNFα on colony formation from CD34+ hematopoietic progenitors and increases hematopoietic colony formation from human isolated MDS progenitors (Sharma et al., 2011). Loss of PKR expression is observed in 5q- and 5q:31-33 myelodysplasias (Green et al., 1999; Giagounidis et al., 2004). |
Disease | Bone marrow failure disorder. |
Prognosis | The presence of p-T451 PKR in the cytoplasm is associated with low-risk disease. The presence of p-T451 PKR in the nucleus is associated with high-risk disease and thus an enhanced probability of progression to acute myelogenous leukemia (AML). Loss of PKR in 5q- and 5q32-33 myelodysplasias is associated with low-risk disease, while loss of PKR in 5q31 myelodysplasias with complex cytogenetics is associated with high-risk disease. |
Oncogenesis | Progression to acute myelogenous leukemia. |
Entity | Fanconi anemia (FA) |
Note | PKR activity is constitutively elevated in bone marrow cells from Fanconi anemia patients and cells lines and contributes to the hypersensitivity of these cells to TNFα and IFNγ (Pang et al., 2001; Zhang et al., 2004). Inhibition of PKR activity by either expressing a dominant negative PKR kinase or a dominant-negative form of the cellular PKR activator RAX/PACT (S18A) reduces apoptosis and sensitivity to TNFα and IFNγ (Pang et al., 2001; Bennett et al., 2006). |
Disease | Bone marrow failure disorder. |
Prognosis | Unknown. |
Oncogenesis | Progression to acute myelogenous leukemia. |
Entity | Acute myelogenous leukemia (AML) |
Note | PKR is overexpressed in blasts from AML patients, and is a functional kinase (Basu et al., 1997). AML derived cell lines contain elevated levels of p-T451 PKR as compared to control peripheral blood lymphocytes (Blalock et al., 2009). AML cell lines were highly dependent on PKR activity for cell maintenance as treatment of the cells with the commercial PKR inhibitor resulted in cell cycle arrest and cell death (Blalock et al., 2009). |
Disease | Cancer; myelo-/monocytic leukemia. |
Prognosis | Unknown. |
Oncogenesis | Contributes to cancer cell maintenance. |
Entity | Acute lymphocytic leukemia (ALL) |
Note | PKR is overexpressed in blasts from ALL patients, and is a functional kinase (Basu et al., 1997). T-ALL derived cell lines contain elevated levels of p-T451 PKR as compared to control peripheral blood lymphocytes (Blalock et al., 2009). T-ALL cell lines were highly dependent on PKR activity for cell maintenance as treatment of the cells with the commercial PKR inhibitor resulted in cell cycle arrest (Blalock et al., 2009). A somatic point mutation was detected in the coding region of dsRNA-binding domain I (coding nucleotide 50 (A to G); amino acid Y17C) of PKR in a patient with T-ALL. Although activation of the mutant PKR kinase by polyI:C was impaired, the exact role of this mutation in the T-ALL was not determined (Murad et al., 2005). |
Disease | Cancer; T-cell derived lymphoblastic leukemia. |
Prognosis | Unknown. |
Cytogenetics | Somatic point mutation in the coding region of dsRNA-binding domain I (coding nucleotide 50 (A to G); amino acid Y17C); Source: T-ALL. |
Oncogenesis | Contributes to cancer cell maintenance. |
Entity | Chronic lymphocytic leukemia (CLL) |
Note | PKR mRNA is underexpressed in CLL as compared to controls, and the kinase is inactive due to the presence of a soluble cellular inhibitor (Basu et al., 1997; Hii et al., 2004). |
Disease | Cancer; B-cell lymphocytic leukemia. |
Prognosis | Unknown. |
Entity | Lung carcinoma |
Note | Elevated phospho-T446 PKR and/or p-S51 eIF2α were associated with longer median survival in patients with non-small cell lung cancer (NSCLC). Combinations of p-PKR/PKR expression or p-eIF2α/PKR expression were valuable prognostic markers for survival (Pataer et al., 2010; He et al., 2011). Lower levels of PKR expression though correlated with aggressive tumor behavior, increased lymph node metastasis and shorter survival in the patients (Pataer et al., 2010). In contrast to NSCLC, a high level of PKR expression was associated with shorter overall survival in patients with small-size lung adenocarcinomas (Roh et al., 2005). |
Disease | Cancer; Non-small cell lung cancer (NSCLC) and small cell adenocarcinoma of the lung. |
Prognosis | PKR expression and activation as determined by immunocytochemistry (p-T446 PKR) are associated with a positive prognosis in NSCLC. PKR expression in small-size lung adenocarcinomas is associated with a poor prognosis. |
Oncogenesis | Low levels of PKR expression favor aggressive behavior and metastasis in NSCLC. |
Entity | Breast carcinoma |
Note | Breast carcinoma cells contain elevated PKR protein and activity (7-40 fold) as compared to controls (Kim et al., 2000; Nussbaum et al., 2003). Stimulation of the PKR promoter ISRE is responsible for enhanced PKR expression (Nussbaum et al., 2003). Elevated PKR activity is further linked to macrophage-migration inhibitory factor (MIF) expression which favors breast cancer cell growth, but also sensitizes breast cancer cells to PKR-mediated killing as the system is already primed (Armstrong et al., 2008; Pervin et al., 2008). PKR may assist in the therapeutic response of 5'Florourocil (5'FU) in p53-null breast cancer (Garcia et al., 2011). |
Disease | Cancer; breast. |
Prognosis | Unknown. |
Oncogenesis | Activated PKR may promote growth of breast carcinoma cells. |
Entity | Colon carcinoma |
Note | Elevated PKR expression and activity are associated with progressive transformation from normal mucosa to adenoma and colon carcinoma (Kim et al., 2002). The activation state of PKR also influences the drug sensitivity of colon cancer cells (Yoon et al., 2009; Yang et al., 2010b; Garcia et al., 2011). |
Disease | Cancer; colon adenoma and colon carcinoma. |
Prognosis | Unknown; associated with progressive transformation and drug-sensitivity. |
Oncogenesis | Progressive transformation to adenomas or carcinomas. |
Entity | Melanoma |
Note | Melanomas contain elevated levels of PKR protein, p-S51 eIF2α and PKR activity as compared to controls (Kim et al., 2002). PKR was highly expressed in melanoma lymph node metastasis (Kim et al., 2002). Knock-down of PKR mRNA and protein in B16-F10 melanoma tumor cells using shRNA led to decreased metastatic nodes in mice (Delgado Andre and De Lucca, 2007). |
Disease | Cancer; skin (melanoma). |
Prognosis | Elevated PKR activity associated with disease progression and metastasis. |
Oncogenesis | Elevated PKR expression and activity are associated with metastasis. |
Entity | Thyroid cancer |
Note | PKR is overexpressed in 90% of thyroid cancers, and its expression is higher in papillary versus nonpapillary carcinoma. Elevated PKR expression was associated with vascular invasion and satellite tumor nodules. PKR expression was linked to a low proliferative activity of the tumor (Terada et al., 2000a). |
Disease | Cancer; thyroid. |
Prognosis | Unknown. |
Oncogenesis | Increased invasiveness and satellite tumor formation. |
Entity | Pancreatic cancer |
Note | PKR is upregulated during interferon treatment of pancreatic cancer where lower PKR expression predicted a shorter anti-cancer response and length of survival following IFN treatment (Zhou et al., 1998). |
Disease | Cancer; neuroendocrine. |
Prognosis | Enhanced expression is associated with a favorable outcome to interferon therapy. Could represent a prognostic indicator. |
Oncogenesis | Role uncharacterized. |
Entity | Gastric cancer |
Note | Levels of phosphorylated forms of PKR and eIF2α were elevated in the rectus abdominus muscle of oesophago-gastric cancer patients as compared to control (Eley et al., 2008). |
Disease | Cancer-related cachexia. |
Prognosis | Poor; Phospho-PKR and Phospho-eIF2α are associated with muscle wasting. |
Entity | Rectal carcinoma |
Note | PKR protein expression is associated with smaller sized tumors, a lower relapse rate and greater 5-year disease-free and overall survival (Kwon et al., 2005). |
Disease | Cancer; lymph node negative rectal carcinoma. |
Prognosis | Favorable; PKR expression is associated with a lower relapse rate and higher disease free and overall survival. |
Oncogenesis | Role uncharacterized. |
Entity | Hepatocellular carcinoma (HCC) |
Note | PKR mRNA and protein are overexpressed and PKR kinase activity enhanced in hepatocellular carcinoma (Hiasa et al., 2003; Alisi et al., 2005). PKR protein levels were observed to increase in bile duct tissue during progression to carcinoma, and this increase was associated with duct inflammation and duct cell proliferation (Terada et al., 2000b). Increased PKR expression was associated with both chronic hepatitis and HCC (Shimada et al., 1998). Importantly, elevated PKR expression is associated with better differentiated HCC and cholangiocarcinoma (Shimada et al., 1998; Terada et al., 2000b). The core protein of hepatitis C virus (HCV), a major contributor to HCC, was seen to bind to and activate PKR (pT446) in HCC cells and tissue (Delhem et al., 2001; Alisi et al., 2005). In contrast, hepatitis B virus infected HCC liver tissue showed decreased PKR expression as determined by real-time PCR and immunohistochemistry and no association between the status of tumor differentiation was observed (Chen et al., 2004). |
Disease | Cancer; hepatocellular carcinoma (HCC) HCV-associated HCC, HBV-associated HCC. |
Oncogenesis | Expression increases with progression toward HCC but is associated with better differentiated tumors (except in HBV-associated HCC). |
Entity | Alzheimer's disease |
Note | Phospho-PKR accumulates in the nuclei of AD brain tissue (Onuki et al., 2004). Neurons from AD patient brains contain elevated levels of p-T446 and/or T451 PKR, and p-S51 eIF2α (Peel and Bredesen, 2003; Suen et al., 2003) and treatment of cell lines with Aβ peptide results in PKR activation, eIF2α phosphorylation and the co-localization of p-PKR with Redd1 and FADD in the nucleus (Suen et al., 2003; Morel et al., 2009b; Couturier et al., 2010a). Phospho-PKR is associated with phospho-Tau and phospho-p38 in AD brain (Peel and Bredesen, 2003). Inhibition of PKR attenuates inflammation as well as TNFα, IL-1α, IL-1β, IL-6 expression and apoptosis stimulated by Aβ peptide (Couturier et al., 2010b; Couturier et al., 2011). Elevated levels of p-PKR, p-eIF2α and secretion of TNFα, IL-1α, IL-1β and IL-6 are observed in peripheral blood mononuclear cells from AD patients (Morel et al., 2009a; Couturier et al., 2010b). |
Disease | Neurodegenerative. |
Prognosis | The presence of elevated p-PKR in brain neuronal tissue is an indicator of cellular stress and degeneration. Possible disease indicator. An EIF2AK2 SNP (C/T; rs2254958) at position 250 in the 5'UTR was found to be associated with Alzheimer's disease (Bullido et al., 2008). |
Cytogenetics | Alzheimer's associated EIF2AK2 SNP (C/T; rs2254958). |
Entity | Parkinson's disease (PD) |
Note | Hippocampal neurons from PD patients contain elevated levels of nuclear p-T446 PKR (Bando et al., 2005). |
Disease | Neurodegenerative. |
Prognosis | Unknown. |
Entity | Huntington chorea |
Note | PKR binds CAG repeats in mutated Huntington transcripts. Affected Huntington tissues contain elevated levels of p-PKR (active) with a particular increase in the nuclei of hippocampal neurons (Peel et al., 2001; Bando et al., 2005). |
Disease | Neurodegenerative. |
Prognosis | Unknown. |
Entity | Creutzfeldt-Jakob disease (CJD) |
Note | Neuronal tissue (frontal, occipital, temporal cortex, striatum and cerebellum) from CJD patients contained elevated levels of p-T451 PKR localized exclusively to the nucleus. The levels of p-T451 PKR were associated with apoptosis, spongiosis, astrocytosis and disease severity (Paquet et al., 2009). |
Disease | Neurodegenerative. |
Prognosis | The levels of p-T451 PKR are associated with disease severity in CJD patients. |
Entity | Amyotrophic lateral sclerosis (ALS) |
Note | The presence of p-T451 PKR increases in spinal cord tissue from ALS patients 2600% (cytosolic) and 3300% (particulate) as compared to controls (Hu et al., 2003). |
Disease | Neurodegenerative. |
Prognosis | Unknown. |
Bibliography |
The murine PKR tumor suppressor gene is rearranged in a lymphocytic leukemia. |
Abraham N, Jaramillo ML, Duncan PI, Methot N, Icely PL, Stojdl DF, Barber GN, Bell JC. |
Exp Cell Res. 1998 Nov 1;244(2):394-404. |
PMID 9806790 |
Thr 446 phosphorylation of PKR by HCV core protein deregulates G2/M phase in HCC cells. |
Alisi A, Mele R, Spaziani A, Tavolaro S, Palescandolo E, Balsano C. |
J Cell Physiol. 2005 Oct;205(1):25-31. |
PMID 15880455 |
Small interfering RNAs induce macrophage migration inhibitory factor production and proliferation in breast cancer cells via a double-stranded RNA-dependent protein kinase-dependent mechanism. |
Armstrong ME, Gantier M, Li L, Chung WY, McCann A, Baugh JA, Donnelly SC. |
J Immunol. 2008 Jun 1;180(11):7125-33. |
PMID 18490711 |
Double-strand RNA dependent protein kinase (PKR) is involved in the extrastriatal degeneration in Parkinson's disease and Huntington's disease. |
Bando Y, Onuki R, Katayama T, Manabe T, Kudo T, Taira K, Tohyama M. |
Neurochem Int. 2005 Jan;46(1):11-8. |
PMID 15567511 |
Role of double-stranded RNA-activated protein kinase in human hematological malignancies. |
Basu S, Panayiotidis P, Hart SM, He LZ, Man A, Hoffbrand AV, Ganeshaguru K. |
Cancer Res. 1997 Mar 1;57(5):943-7. |
PMID 9041199 |
The RAX/PACT-PKR stress response pathway promotes p53 sumoylation and activation, leading to G1 arrest. |
Bennett RL, Pan Y, Christian J, Hui T, May WS Jr. |
Cell Cycle. 2012 Jan 15;11(2):407-17. Epub 2012 Jan 15. |
PMID 22214662 |
Characterization of a mammalian homolog of the GCN2 eukaryotic initiation factor 2alpha kinase. |
Berlanga JJ, Santoyo J, De Haro C. |
Eur J Biochem. 1999 Oct;265(2):754-62. |
PMID 10504407 |
PKR activity is required for acute leukemic cell maintenance and growth: a role for PKR-mediated phosphatase activity to regulate GSK-3 phosphorylation. |
Blalock WL, Grimaldi C, Fala F, Follo M, Horn S, Basecke J, Martinelli G, Cocco L, Martelli AM. |
J Cell Physiol. 2009 Oct;221(1):232-41. |
PMID 19507191 |
The N-terminus of PKR is responsible for the activation of the NF-kappaB signaling pathway by interacting with the IKK complex. |
Bonnet MC, Daurat C, Ottone C, Meurs EF. |
Cell Signal. 2006 Nov;18(11):1865-75. Epub 2006 Feb 28. |
PMID 16600570 |
PKR stimulates NF-kappaB irrespective of its kinase function by interacting with the IkappaB kinase complex. |
Bonnet MC, Weil R, Dam E, Hovanessian AG, Meurs EF. |
Mol Cell Biol. 2000 Jul;20(13):4532-42. |
PMID 10848580 |
Double stranded RNA activated EIF2 alpha kinase (EIF2AK2; PKR) is associated with Alzheimer's disease. |
Bullido MJ, Martinez-Garcia A, Tenorio R, Sastre I, Munoz DG, Frank A, Valdivieso F. |
Neurobiol Aging. 2008 Aug;29(8):1160-6. Epub 2007 Apr 8. |
PMID 17420072 |
Reduction of double-stranded RNA-activated protein kinase in hepatocellular carcinoma associated with hepatitis B virus. |
Chen GG, Lai PB, Ho RL, Chan PK, Xu H, Wong J, Lau WY. |
J Med Virol. 2004 Jun;73(2):187-94. |
PMID 15122791 |
Regulation of protein synthesis by the heme-regulated eIF2alpha kinase: relevance to anemias. |
Chen JJ. |
Blood. 2007 Apr 1;109(7):2693-9. (REVIEW) |
PMID 17110456 |
Quantitative phosphoproteomics dissection of seven-transmembrane receptor signaling using full and biased agonists. |
Christensen GL, Kelstrup CD, Lyngso C, Sarwar U, Bogebo R, Sheikh SP, Gammeltoft S, Olsen JV, Hansen JL. |
Mol Cell Proteomics. 2010 Jul;9(7):1540-53. Epub 2010 Apr 2. |
PMID 20363803 |
Structure and regulation of eukaryotic initiation factor eIF-2. Sequence of the site in the alpha subunit phosphorylated by the haem-controlled repressor and by the double-stranded RNA-activated inhibitor. |
Colthurst DR, Campbell DG, Proud CG. |
Eur J Biochem. 1987 Jul 15;166(2):357-63. |
PMID 3609013 |
Prevention of the beta-amyloid peptide-induced inflammatory process by inhibition of double-stranded RNA-dependent protein kinase in primary murine mixed co-cultures. |
Couturier J, Paccalin M, Morel M, Terro F, Milin S, Pontcharraud R, Fauconneau B, Page G. |
J Neuroinflammation. 2011 Jun 23;8:72. |
PMID 21699726 |
The double-stranded RNA activated protein kinase PKR physically associates with the tumor suppressor p53 protein and phosphorylates human p53 on serine 392 in vitro. |
Cuddihy AR, Wong AH, Tam NW, Li S, Koromilas AE. |
Oncogene. 1999 Apr 29;18(17):2690-702. |
PMID 10348343 |
Protein kinase PKR is required for platelet-derived growth factor signaling of c-fos gene expression via Erks and Stat3. |
Deb A, Zamanian-Daryoush M, Xu Z, Kadereit S, Williams BR. |
EMBO J. 2001 May 15;20(10):2487-96. |
PMID 11350938 |
Knockdown of PKR expression by RNAi reduces pulmonary metastatic potential of B16-F10 melanoma cells in mice: possible role of NF-kappaB. |
Delgado Andre N, De Lucca FL. |
Cancer Lett. 2007 Dec 8;258(1):118-25. |
PMID 17936498 |
Activation of the interferon-inducible protein kinase PKR by hepatocellular carcinoma derived-hepatitis C virus core protein. |
Delhem N, Sabile A, Gajardo R, Podevin P, Abadie A, Blaton MA, Kremsdorf D, Beretta L, Brechot C. |
Oncogene. 2001 Sep 13;20(41):5836-45. |
PMID 11593389 |
A quantitative atlas of mitotic phosphorylation. |
Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP. |
Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. Epub 2008 Jul 31. |
PMID 18669648 |
The protein kinase PKR: a molecular clock that sequentially activates survival and death programs. |
Donze O, Deng J, Curran J, Sladek R, Picard D, Sonenberg N. |
EMBO J. 2004 Feb 11;23(3):564-71. Epub 2004 Jan 29. |
PMID 14749731 |
Inhibition of activation of dsRNA-dependent protein kinase and tumour growth inhibition. |
Eley HL, McDonald PS, Russell ST, Tisdale MJ. |
Cancer Chemother Pharmacol. 2009 Mar;63(4):651-9. Epub 2008 Jun 14. |
PMID 18553083 |
Increased expression of phosphorylated forms of RNA-dependent protein kinase and eukaryotic initiation factor 2alpha may signal skeletal muscle atrophy in weight-losing cancer patients. |
Eley HL, Skipworth RJ, Deans DA, Fearon KC, Tisdale MJ. |
Br J Cancer. 2008 Jan 29;98(2):443-9. Epub 2007 Dec 18. |
PMID 18087277 |
Regulation of internal ribosome entry site-mediated translation by eukaryotic initiation factor-2alpha phosphorylation and translation of a small upstream open reading frame. |
Fernandez J, Yaman I, Merrick WC, Koromilas A, Wek RC, Sood R, Hensold J, Hatzoglou M. |
J Biol Chem. 2002 Jan 18;277(3):2050-8. Epub 2001 Oct 29. |
PMID 11684693 |
PKR is activated in MDS patients and its subcellular localization depends on disease severity. |
Follo MY, Finelli C, Mongiorgi S, Clissa C, Bosi C, Martinelli G, Blalock WL, Cocco L, Martelli AM. |
Leukemia. 2008 Dec;22(12):2267-9. Epub 2008 May 22. |
PMID 18496558 |
The chemotherapeutic drug 5-fluorouracil promotes PKR-mediated apoptosis in a p53-independent manner in colon and breast cancer cells. |
Garcia MA, Carrasco E, Aguilera M, Alvarez P, Rivas C, Campos JM, Prados JC, Calleja MA, Esteban M, Marchal JA, Aranega A. |
PLoS One. 2011;6(8):e23887. Epub 2011 Aug 24. |
PMID 21887339 |
Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. |
Garcia MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, Esteban M. |
Microbiol Mol Biol Rev. 2006 Dec;70(4):1032-60. (REVIEW) |
PMID 17158706 |
The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |
Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J; MGC Project Team. |
Genome Res. 2004 Oct;14(10B):2121-7. |
PMID 15489334 |
Phosphorylation of initiation factor-2 alpha is required for activation of internal translation initiation during cell differentiation. |
Gerlitz G, Jagus R, Elroy-Stein O. |
Eur J Biochem. 2002 Jun;269(11):2810-9. |
PMID 12047392 |
Clinical, morphological, cytogenetic, and prognostic features of patients with myelodysplastic syndromes and del(5q) including band q31. |
Giagounidis AA, Germing U, Haase S, Hildebrandt B, Schlegelberger B, Schoch C, Wilkens L, Heinsch M, Willems H, Aivado M, Aul C. |
Leukemia. 2004 Jan;18(1):113-9. |
PMID 14586479 |
Activation of NF-kappa B by the dsRNA-dependent protein kinase, PKR involves the I kappa B kinase complex. |
Gil J, Alcami J, Esteban M. |
Oncogene. 2000 Mar 9;19(11):1369-78. |
PMID 10723127 |
Lack of IRF-1 expression in acute promyelocytic leukemia and in a subset of acute myeloid leukemias with del(5)(q31). |
Green WB, Slovak ML, Chen IM, Pallavicini M, Hecht JL, Willman CL. |
Leukemia. 1999 Dec;13(12):1960-71. |
PMID 10602416 |
The role of PKR/eIF2? signaling pathway in prognosis of non-small cell lung cancer. |
He Y, Correa AM, Raso MG, Hofstetter WL, Fang B, Behrens C, Roth JA, Zhou Y, Yu L, Wistuba II, Swisher SG, Pataer A. |
PLoS One. 2011;6(11):e24855. Epub 2011 Nov 10. |
PMID 22102852 |
Protein kinase R is increased and is functional in hepatitis C virus-related hepatocellular carcinoma. |
Hiasa Y, Kamegaya Y, Nuriya H, Onji M, Kohara M, Schmidt EV, Chung RT. |
Am J Gastroenterol. 2003 Nov;98(11):2528-34. |
PMID 14638359 |
Loss of PKR activity in chronic lymphocytic leukemia. |
Hii SI, Hardy L, Crough T, Payne EJ, Grimmett K, Gill D, McMillan NA. |
Int J Cancer. 2004 Apr 10;109(3):329-35. |
PMID 14961569 |
Protein kinase and protein phosphatase expression in amyotrophic lateral sclerosis spinal cord. |
Hu JH, Zhang H, Wagey R, Krieger C, Pelech SL. |
J Neurochem. 2003 Apr;85(2):432-42. |
PMID 12675919 |
IFN-gamma-induced upregulation of Fcgamma-receptor-I during activation of monocytic cells requires the PKR and NFkappaB pathways. |
Karehed K, Dimberg A, Dahl S, Nilsson K, Oberg F. |
Mol Immunol. 2007 Jan;44(4):615-24. Epub 2006 Mar 3. |
PMID 16516295 |
Alternative splice variants of the human PKR protein kinase possessing different 5'-untranslated regions: expression in untreated and interferon-treated cells and translational activity. |
Kawakubo K, Kuhen KL, Vessey JW, George CX, Samuel CE. |
Virology. 1999 Nov 10;264(1):106-14. |
PMID 10544135 |
A DNA damage-induced p53 serine 392 kinase complex contains CK2, hSpt16, and SSRP1. |
Keller DM, Zeng X, Wang Y, Zhang QH, Kapoor M, Shu H, Goodman R, Lozano G, Zhao Y, Lu H. |
Mol Cell. 2001 Feb;7(2):283-92. |
PMID 11239457 |
Human breast cancer cells contain elevated levels and activity of the protein kinase, PKR. |
Kim SH, Forman AP, Mathews MB, Gunnery S. |
Oncogene. 2000 Jun 22;19(27):3086-94. |
PMID 10871861 |
Neoplastic progression in melanoma and colon cancer is associated with increased expression and activity of the interferon-inducible protein kinase, PKR. |
Kim SH, Gunnery S, Choe JK, Mathews MB. |
Oncogene. 2002 Dec 12;21(57):8741-8. |
PMID 12483527 |
Systematic and quantitative assessment of the ubiquitin-modified proteome. |
Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP. |
Mol Cell. 2011 Oct 21;44(2):325-40. Epub 2011 Sep 8. |
PMID 21906983 |
Regulation of guanine nucleotide exchange through phosphorylation of eukaryotic initiation factor eIF2alpha. Role of the alpha- and delta-subunits of eiF2b. |
Kimball SR, Fabian JR, Pavitt GD, Hinnebusch AG, Jefferson LS. |
J Biol Chem. 1998 May 22;273(21):12841-5. |
PMID 9582312 |
CDDO induces granulocytic differentiation of myeloid leukemic blasts through translational up-regulation of p42 CCAAT enhancer binding protein alpha. |
Koschmieder S, D'Alo F, Radomska H, Schoneich C, Chang JS, Konopleva M, Kobayashi S, Levantini E, Suh N, Di Ruscio A, Voso MT, Watt JC, Santhanam R, Sargin B, Kantarjian H, Andreeff M, Sporn MB, Perrotti D, Berdel WE, Muller-Tidow C, Serve H, Tenen DG. |
Blood. 2007 Nov 15;110(10):3695-705. Epub 2007 Aug 1. |
PMID 17671235 |
Tight binding of the phosphorylated alpha subunit of initiation factor 2 (eIF2alpha) to the regulatory subunits of guanine nucleotide exchange factor eIF2B is required for inhibition of translation initiation. |
Krishnamoorthy T, Pavitt GD, Zhang F, Dever TE, Hinnebusch AG. |
Mol Cell Biol. 2001 Aug;21(15):5018-30. |
PMID 11438658 |
Mechanism of interferon action: functional characterization of positive and negative regulatory domains that modulate transcriptional activation of the human RNA-dependent protein kinase Pkr promoter. |
Kuhen KL, Samuel CE. |
Virology. 1999 Feb 1;254(1):182-95. |
PMID 9927585 |
Structural organization of the human gene (PKR) encoding an interferon-inducible RNA-dependent protein kinase (PKR) and differences from its mouse homolog. |
Kuhen KL, Shen X, Carlisle ER, Richardson AL, Weier HU, Tanaka H, Samuel CE. |
Genomics. 1996 Aug 15;36(1):197-201. |
PMID 8812437 |
Mechanism of interferon action: identification of essential positions within the novel 15-base-pair KCS element required for transcriptional activation of the RNA-dependent protein kinase pkr gene. |
Kuhen KL, Vessey JW, Samuel CE. |
J Virol. 1998 Dec;72(12):9934-9. |
PMID 9811730 |
Expression of double-stranded RNA-activated protein kinase (PKR) and its prognostic significance in lymph node negative rectal cancer. |
Kwon HC, Moon CH, Kim SH, Choi HJ, Lee HS, Roh MS, Hwang TH, Kim JS, Kim HJ. |
Jpn J Clin Oncol. 2005 Sep;35(9):545-50. Epub 2005 Sep 7. |
PMID 16148023 |
An upstream open reading frame regulates translation of GADD34 during cellular stresses that induce eIF2alpha phosphorylation. |
Lee YY, Cevallos RC, Jan E. |
J Biol Chem. 2009 Mar 13;284(11):6661-73. Epub 2009 Jan 8. |
PMID 19131336 |
The interferon-induced double-stranded RNA-activated protein kinase PKR will phosphorylate serine, threonine, or tyrosine at residue 51 in eukaryotic initiation factor 2alpha. |
Lu J, O'Hara EB, Trieselmann BA, Romano PR, Dever TE. |
J Biol Chem. 1999 Nov 5;274(45):32198-203. |
PMID 10542257 |
Evidence of molecular links between PKR and mTOR signalling pathways in Abeta neurotoxicity: role of p53, Redd1 and TSC2. |
Morel M, Couturier J, Pontcharraud R, Gil R, Fauconneau B, Paccalin M, Page G. |
Neurobiol Dis. 2009b Oct;36(1):151-61. Epub 2009 Jul 23. |
PMID 19631745 |
A point mutation in the RNA-binding domain I results in decrease of PKR activation in acute lymphoblastic leukemia. |
Murad JM, Tone LG, de Souza LR, De Lucca FL. |
Blood Cells Mol Dis. 2005 Jan-Feb;34(1):1-5. |
PMID 15607693 |
Double-stranded RNA-dependent protein kinase links pathogen sensing with stress and metabolic homeostasis. |
Nakamura T, Furuhashi M, Li P, Cao H, Tuncman G, Sonenberg N, Gorgun CZ, Hotamisligil GS. |
Cell. 2010 Feb 5;140(3):338-48. |
PMID 20144759 |
Biochemical analysis of the eIF2beta gamma complex reveals a structural function for eIF2alpha in catalyzed nucleotide exchange. |
Nika J, Rippel S, Hannig EM. |
J Biol Chem. 2001 Jan 12;276(2):1051-6. |
PMID 11042214 |
Transcriptional upregulation of interferon-induced protein kinase, PKR, in breast cancer. |
Nussbaum JM, Major M, Gunnery S. |
Cancer Lett. 2003 Jul 10;196(2):207-16. |
PMID 12860279 |
Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. |
Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M. |
Sci Signal. 2010 Jan 12;3(104):ra3. |
PMID 20068231 |
An RNA-dependent protein kinase is involved in tunicamycin-induced apoptosis and Alzheimer's disease. |
Onuki R, Bando Y, Suyama E, Katayama T, Kawasaki H, Baba T, Tohyama M, Taira K. |
EMBO J. 2004 Feb 25;23(4):959-68. Epub 2004 Feb 5. |
PMID 14765129 |
Role of double-stranded RNA-dependent protein kinase in mediating hypersensitivity of Fanconi anemia complementation group C cells to interferon gamma, tumor necrosis factor-alpha, and double-stranded RNA. |
Pang Q, Keeble W, Diaz J, Christianson TA, Fagerlie S, Rathbun K, Faulkner GR, O'Dwyer M, Bagby GC Jr. |
Blood. 2001 Mar 15;97(6):1644-52. |
PMID 11238103 |
Neuronal phosphorylated RNA-dependent protein kinase in Creutzfeldt-Jakob disease. |
Paquet C, Bose A, Polivka M, Peoc'h K, Brouland JP, Keohane C, Hugon J, Gray F. |
J Neuropathol Exp Neurol. 2009 Feb;68(2):190-8. |
PMID 19151623 |
Prognostic significance of RNA-dependent protein kinase on non-small cell lung cancer patients. |
Pataer A, Raso MG, Correa AM, Behrens C, Tsuta K, Solis L, Fang B, Roth JA, Wistuba II, Swisher SG. |
Clin Cancer Res. 2010 Nov 15;16(22):5522-8. Epub 2010 Oct 7. |
PMID 20930042 |
Activation of the cell stress kinase PKR in Alzheimer's disease and human amyloid precursor protein transgenic mice. |
Peel AL, Bredesen DE. |
Neurobiol Dis. 2003 Oct;14(1):52-62. |
PMID 13678666 |
Double-stranded RNA-dependent protein kinase, PKR, binds preferentially to Huntington's disease (HD) transcripts and is activated in HD tissue. |
Peel AL, Rao RV, Cottrell BA, Hayden MR, Ellerby LM, Bredesen DE. |
Hum Mol Genet. 2001 Jul 15;10(15):1531-8. |
PMID 11468270 |
PKR activation in neurodegenerative disease. |
Peel AL. |
J Neuropathol Exp Neurol. 2004 Feb;63(2):97-105. (REVIEW) |
PMID 14989595 |
Increased susceptibility of breast cancer cells to stress mediated inhibition of protein synthesis. |
Pervin S, Tran AH, Zekavati S, Fukuto JM, Singh R, Chaudhuri G. |
Cancer Res. 2008 Jun 15;68(12):4862-74. |
PMID 18559534 |
Regulation of c-myc expression by IFN-gamma through Stat1-dependent and -independent pathways. |
Ramana CV, Grammatikakis N, Chernov M, Nguyen H, Goh KC, Williams BR, Stark GR. |
EMBO J. 2000 Jan 17;19(2):263-72. |
PMID 10637230 |
Interferon-mediated protein kinase and low-molecular-weight inhibitor of protein synthesis. |
Roberts WK, Hovanessian A, Brown RE, Clemens MJ, Kerr IM. |
Nature. 1976a Dec 2;264(5585):477-80. |
PMID 1004583 |
Expression of double-stranded RNA-activated protein kinase in small-size peripheral adenocarcinoma of the lung. |
Roh MS, Kwak JY, Kim SJ, Lee HW, Kwon HC, Hwang TH, Choi PJ, Hong YS. |
Pathol Int. 2005 Nov;55(11):688-93. |
PMID 16271080 |
Autophosphorylation in the activation loop is required for full kinase activity in vivo of human and yeast eukaryotic initiation factor 2alpha kinases PKR and GCN2. |
Romano PR, Garcia-Barrio MT, Zhang X, Wang Q, Taylor DR, Zhang F, Herring C, Mathews MB, Qin J, Hinnebusch AG. |
Mol Cell Biol. 1998 Apr;18(4):2282-97. |
PMID 9528799 |
PKR regulates B56(alpha)-mediated BCL2 phosphatase activity in acute lymphoblastic leukemia-derived REH cells. |
Ruvolo VR, Kurinna SM, Karanjeet KB, Schuster TF, Martelli AM, McCubrey JA, Ruvolo PP. |
J Biol Chem. 2008 Dec 19;283(51):35474-85. Epub 2008 Oct 28. |
PMID 18957415 |
An antiviral response directed by PKR phosphorylation of the RNA helicase A. |
Sadler AJ, Latchoumanin O, Hawkes D, Mak J, Williams BR. |
PLoS Pathog. 2009 Feb;5(2):e1000311. Epub 2009 Feb 20. |
PMID 19229320 |
Phosphorylation of serine 392 stabilizes the tetramer formation of tumor suppressor protein p53. |
Sakaguchi K, Sakamoto H, Lewis MS, Anderson CW, Erickson JW, Appella E, Xie D. |
Biochemistry. 1997 Aug 19;36(33):10117-24. |
PMID 9254608 |
Protein kinase R as mediator of the effects of interferon (IFN) gamma and tumor necrosis factor (TNF) alpha on normal and dysplastic hematopoiesis. |
Sharma B, Altman JK, Goussetis DJ, Verma AK, Platanias LC. |
J Biol Chem. 2011 Aug 5;286(31):27506-14. Epub 2011 Jun 9. |
PMID 21659535 |
Identification and characterization of pancreatic eukaryotic initiation factor 2 alpha-subunit kinase, PEK, involved in translational control. |
Shi Y, Vattem KM, Sood R, An J, Liang J, Stramm L, Wek RC. |
Mol Cell Biol. 1998 Dec;18(12):7499-509. |
PMID 9819435 |
Aberrant expression of double-stranded RNA-dependent protein kinase in hepatocytes of chronic hepatitis and differentiated hepatocellular carcinoma. |
Shimada A, Shiota G, Miyata H, Kamahora T, Kawasaki H, Shiraki K, Hino S, Terada T. |
Cancer Res. 1998 Oct 1;58(19):4434-8. |
PMID 9766675 |
Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2. |
Su Q, Wang S, Baltzis D, Qu LK, Raven JF, Li S, Wong AH, Koromilas AE. |
EMBO Rep. 2007 Mar;8(3):265-70. Epub 2007 Feb 9. |
PMID 17290288 |
Phosphorylation of serine 51 in initiation factor 2 alpha (eIF2 alpha) promotes complex formation between eIF2 alpha(P) and eIF2B and causes inhibition in the guanine nucleotide exchange activity of eIF2B. |
Sudhakar A, Ramachandran A, Ghosh S, Hasnain SE, Kaufman RJ, Ramaiah KV. |
Biochemistry. 2000 Oct 24;39(42):12929-38. |
PMID 11041858 |
Upstream signaling pathways leading to the activation of double-stranded RNA-dependent serine/threonine protein kinase in beta-amyloid peptide neurotoxicity. |
Suen KC, Yu MS, So KF, Chang RC, Hugon J. |
J Biol Chem. 2003 Dec 12;278(50):49819-27. Epub 2003 Sep 15. |
PMID 12975376 |
Hepatitis C virus envelope protein E2 does not inhibit PKR by simple competition with autophosphorylation sites in the RNA-binding domain. |
Taylor DR, Tian B, Romano PR, Hinnebusch AG, Lai MM, Mathews MB. |
J Virol. 2001 Feb;75(3):1265-73. |
PMID 11152499 |
Protein expression of double-stranded RNA-activated protein kinase in thyroid carcinomas: correlations with histologic types, pathologic parameters, and Ki-67 labeling. |
Terada T, Maeta H, Endo K, Ohta T. |
Hum Pathol. 2000a Jul;31(7):817-21. |
PMID 10923918 |
Protein expression of double-stranded RNA-activated protein kinase (PKR) in intrahepatic bile ducts in normal adult livers, fetal livers, primary biliary cirrhosis, hepatolithiasis and intrahepatic cholangiocarcinoma. |
Terada T, Ueyama J, Ukita Y, Ohta T. |
Liver. 2000b Dec;20(6):450-7. |
PMID 11169059 |
A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles. |
Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C. |
Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. Epub 2011 Sep 1. |
PMID 21890473 |
The PKR kinase promoter binds both Sp1 and Sp3, but only Sp3 functions as part of the interferon-inducible complex with ISGF-3 proteins. |
Ward SV, Samuel CE. |
Virology. 2003 Sep 1;313(2):553-66. |
PMID 12954221 |
Coping with stress: eIF2 kinases and translational control. |
Wek RC, Jiang HY, Anthony TG. |
Biochem Soc Trans. 2006 Feb;34(Pt 1):7-11. (REVIEW) |
PMID 16246168 |
PKR; a sentinel kinase for cellular stress. |
Williams BR. |
Oncogene. 1999 Nov 1;18(45):6112-20. (REVIEW) |
PMID 10557102 |
Physical association between STAT1 and the interferon-inducible protein kinase PKR and implications for interferon and double-stranded RNA signaling pathways. |
Wong AH, Tam NW, Yang YL, Cuddihy AR, Li S, Kirchhoff S, Hauser H, Decker T, Koromilas AE. |
EMBO J. 1997 Mar 17;16(6):1291-304. |
PMID 9135145 |
The B56alpha regulatory subunit of protein phosphatase 2A is a target for regulation by double-stranded RNA-dependent protein kinase PKR. |
Xu Z, Williams BR. |
Mol Cell Biol. 2000 Jul;20(14):5285-99. |
PMID 10866685 |
The zipper model of translational control: a small upstream ORF is the switch that controls structural remodeling of an mRNA leader. |
Yaman I, Fernandez J, Liu H, Caprara M, Komar AA, Koromilas AE, Zhou L, Snider MD, Scheuner D, Kaufman RJ, Hatzoglou M. |
Cell. 2003 May 16;113(4):519-31. |
PMID 12757712 |
The integrated stress response-associated signals modulates intestinal tumor cell growth by NSAID-activated gene 1 (NAG-1/MIC-1/PTGF-beta). |
Yang H, Park SH, Choi HJ, Moon Y. |
Carcinogenesis. 2010b Apr;31(4):703-11. Epub 2010 Feb 3. |
PMID 20130018 |
The double-stranded RNA-dependent protein kinase differentially regulates insulin receptor substrates 1 and 2 in HepG2 cells. |
Yang X, Nath A, Opperman MJ, Chan C. |
Mol Biol Cell. 2010a Oct 1;21(19):3449-58. Epub 2010 Aug 4. |
PMID 20685959 |
PKR, a p53 target gene, plays a crucial role in the tumor-suppressor function of p53. |
Yoon CH, Lee ES, Lim DS, Bae YS. |
Proc Natl Acad Sci U S A. 2009 May 12;106(19):7852-7. Epub 2009 Apr 24. |
PMID 19416861 |
New Cdc2 Tyr 4 phosphorylation by dsRNA-activated protein kinase triggers Cdc2 polyubiquitination and G2 arrest under genotoxic stresses. |
Yoon CH, Miah MA, Kim KP, Bae YS. |
EMBO Rep. 2010 May;11(5):393-9. Epub 2010 Apr 16. |
PMID 20395957 |
NF-kappaB activation by double-stranded-RNA-activated protein kinase (PKR) is mediated through NF-kappaB-inducing kinase and IkappaB kinase. |
Zamanian-Daryoush M, Mogensen TH, DiDonato JA, Williams BR. |
Mol Cell Biol. 2000 Feb;20(4):1278-90. |
PMID 10648614 |
Binding of double-stranded RNA to protein kinase PKR is required for dimerization and promotes critical autophosphorylation events in the activation loop. |
Zhang F, Romano PR, Nagamura-Inoue T, Tian B, Dever TE, Mathews MB, Ozato K, Hinnebusch AG. |
J Biol Chem. 2001 Jul 6;276(27):24946-58. Epub 2001 May 3. |
PMID 11337501 |
The Fanconi anemia proteins functionally interact with the protein kinase regulated by RNA (PKR). |
Zhang X, Li J, Sejas DP, Rathbun KR, Bagby GC, Pang Q. |
J Biol Chem. 2004 Oct 15;279(42):43910-9. Epub 2004 Aug 6. |
PMID 15299030 |
Expression of p68 protein kinase and its prognostic significance during IFN-alpha therapy in patients with carcinoid tumours. |
Zhou Y, Gobl A, Wang S, Jacobsen MB, Janson ET, Haines GK 3rd, Radosevich JA, Oberg K. |
Eur J Cancer. 1998 Dec;34(13):2046-52. |
PMID 10070309 |
Regulation of Cited2 expression provides a functional link between translational and transcriptional responses during hypoxia. |
van den Beucken T, Magagnin MG, Savelkouls K, Lambin P, Koritzinsky M, Wouters BG. |
Radiother Oncol. 2007 Jun;83(3):346-52. Epub 2007 May 17. |
PMID 17499866 |
Citation |
This paper should be referenced as such : |
Blalock, WL ; Cocco, L |
EIF2AK2 (eukaryotic translation initiation factor 2-alpha kinase 2) |
Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):601-613. |
Free journal version : [ pdf ] [ DOI ] |
On line version : http://AtlasGeneticsOncology.org/Genes/EIF2AK2ID41866ch2p22.html |
Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 2 ] |
EIF2AK2/CEBPZ (2p22)
EIF2AK2/RMDN2 (2p22) |
External links |
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Last year publications | automatic search in PubMed |
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