Recombinant Mouse Eukaryotic translation initiation factor 2-alpha kinase 4 (Eif2ak4), partial

1. our data provide solid evidence that GCN2 has a marked effect on Dox induced myocardial apoptosis and oxidative stress. Our findings suggest that strategies to inhibit GCN2 activity in cardiomyocyte may provide a novel approach to attenuate Dox-related cardiotoxicity. PMID: 29660505
2. heme-regulated inhibitor (HRI), protein kinase R (PKR), PKR-like endoplasmic reticulum kinase, (PERK) and general control non-depressible 2 (GCN2) are sufficient for the integrated stress response; there are no additional eIF2alpha kinases in vertebrates PMID: 27633668
3. These data point to a novel role for GCN2 and phosphorylation of eIF2alpha in the control of mTORC1 by certain amino acids. PMID: 27297692
4. We hypothesize that the essential role of methionine-charged initiator tRNA in forming ternary complex is responsible for the robust ability of methionine deficiency to induce ATF4 and the ISR even in the absence of GCN2 or eIF2alpha kinase activity. PMID: 27613409
5. GCN2 is only transiently required for LP-induced FGF21. PMID: 27396336
6. GCN2 is required for normal cytotoxic T cell function. PMID: 27880901
7. The data of this study suggest an important contribution of the General control non-derepressible 2 (GCN2) in T cell stress response to the resolution of autoimmune neuroinflammation. PMID: 27397084
8. GCN2 activation increased phosphorylation of its substrate eIF2alpha and the induction of the integrated stress response master regulator, ATF4. PMID: 27852836
9. GCN2 predisposes the exocrine pancreas to a maladaptive ER stress response and autophagy during asparaginase treatment. PMID: 26968207
10. Inhibition of eIF2alpha phosphorylation via PERK suppression and reversal of de novo protein synthesis deficits can mitigate cognitive deficits in neurodegenerative diseases. PMID: 27103515
11. Dietary EAA sensing depends on physiologic need, but not GCN2. PMID: 26526991
12. Targeting ALDH18A1 activated the serine/threonine protein kinase GCN2 (general control nonderepressible 2) to inhibit protein synthesis in melanoma. PMID: 26082174
13. acute amino acid starvation suppressed intestinal inflammation via a mechanism dependent on GCN2; hence, results reveal a mechanism that couples amino acid sensing with control of intestinal inflammation via GCN2 PMID: 26982722
14. Gcn2 & Atf4 are involved in L-proline metabolism regulation in embryonic stem cells. PMID: 25857264
15. Metabolic stress signals delivered by GCN2 inhibit innate inflammatory responses to apoptotic cells, restricting adaptive immunity and preventing autoimmunity. GCN2 activation by halofunginone halobromide potently reduced autoimmune reactivity. PMID: 26261340
16. p58IPK is a general inhibitor of the eIF2alpha kinases in that it also interacts with GCN2. Thus forced overexpression of cytoplasmic p58 delays eIF2alpha phosphorylation, suppresses GCN2 phosphorylation and prolongs protein synthesis PMID: 25329545
17. Data indicate that the crystal structures of murine and yeast GCN2 protein kinase C-terminal domain (CTD) showed dimers. PMID: 24719324
18. The results suggest that the GCN2 kinase-dependent sensing of indoleamine 2,3-dioxygenase activity represents an important trigger to the experimental autoimmune encephalomyelitis remission phase. PMID: 24362236
19. Deletion of the eIF2alpha Kinase GCN2 fails to rescue the memory decline associated with Alzheimer's disease. PMID: 24146979
20. The present study provides the first direct evidence that inhibition of GCN2 activity by GCN2 gene deletion attenuates the development of heart failure. PMID: 24166753
21. Data indicate that the GCN2 knockout mice showed reduced inflammatory responses, with decreased IL-6 and IL-12 expression correlating with significant reduction in animal mortality. PMID: 24248597
22. This study extends our understanding of the roles played by GCN1 in GCN2 activation induced by a variety of stress arrangements and suggests that IMPACT and YIH1 use similar mechanisms for regulating this eIF2alpha kinase. PMID: 24333428
23. GCN2 protects the brain from developing a lethal leukodystrophy in response to amino acid deficiencies. PMID: 24019515
24. Data from knockout mice suggest that GCN2 (general control nondepressible-2) is important in maintaining gluconeogenesis in the liver; this effect is likely mediated through regulation of expression of Cebpb (CCAAT enhancer binding protein beta). PMID: 23900421
25. Many genes with important functions in protein synthesis/degradation, transcriptional regulation and apoptosis were induced by NaSal and most of these were dependent on GCN2. PMID: 23356852
26. the participation of the GCN2-IMPACT module of translational regulation in a highly controlled step in the development of the nervous system. PMID: 23447528
27. GCN2 kinase is a key regulator of fibrogenesis and acute and chronic liver injury induced by carbon tetrachloride in mice. PMID: 23318883
28. Both dietary and pharmacological interventions required the amino acid sensor and eIF2alpha kinase Gcn2, implicating the amino acid starvation response and translational control in stress protection. PMID: 22277968
29. High dosage of resveratrol pretreatment inhibited the injury-induced up-regulation of eIF2alpha-CHOP and IRE1alpha-XBP1 pathways. PMID: 22491413
30. Data from GCN2 knockout mice suggest that GCN2 participates in the control of food preferences; studies address role of GCN2 in macronutrient selection and its age-related changes. PMID: 21614613
31. describe the recessive, loss-of-function mutation atchoum (atc) in Eif2ak4, encoding GCN2, which increased susceptibility to infection by the double-stranded DNA viruses mouse cytomegalovirus (MCMV) and human adenovirus PMID: 22114338
32. It was shown that urea-inducible GCN2 activation initiates the phosphorylation of eIF2alpha and the downstream increase of activating transcription factor 3. PMID: 21880833
33. GCN2 and its downstream signaling pathway have an important role in the protection against oxidative injuries induced by an amino acid-imbalanced diet, and that it can play a critical role in the prevention of oxidative damage PMID: 22020073
34. PERK and GCN2 also have a functional role on regulating translation under non-stressed conditions, apart from their long established roles as stress kinases. PMID: 21638082
35. amino acid starvation was able to induce p8 expression; GCN2/ATF4 pathway is involved in this regulation through the presence of an Amino Acid Response Element in p8 promoter. PMID: 21867687
36. the GCN2/eIF2alpha/ATF4 pathway is essential for the induction of the TRB3 gene transcription PMID: 21203563
37. the effects of arginine deficiency were solely mediated by GCN2 PMID: 21239484
38. The eIF2alpha kinases PKR and GCN2 promote apoptosis. PMID: 21076179
39. Results from knockout mice emphasize importance of GCN2 in adaptation of immune system in amino acid starvation/deprivation. PMID: 20861212
40. Data show that reduced phosphorylation of eIF2alpha by knocking out either PERK or GCN2 suppresses hypoxia-induced G(1) arrest and promotes apoptosis in accompany with activation of p53 signal cascade. PMID: 20072654
41. Data demonstrated that eIF2alpha kinases GCN2 and PERK differentially regulate mRNA transcription and translation, which in the latter case suggests that increased eIF2alpha phosphorylation is not sufficient for derepression of translation. PMID: 19509078
42. regulated translation initiation controls stress-induced gene expression in mammalian cells PMID: 11106749
43. activation in UV-irradiated cells inhibits translation PMID: 12176355
44. GCN2 has a role in maintaining protein mass in skeletal muscle and liver PMID: 15213227
45. reported that the mechanism for recognizing indispensable amino acid-deficient foods follows the conserved general control system, wherein uncharged transfer RNA induces phosphorylation of eukaryotic initiation factor 2 alpha via the GCN2 kinase PMID: 15774759
46. GCN2 acts as a molecular sensor in T cells, allowing them to detect and respond to conditions created by indoleamine 2,3-dioxygenase. PMID: 15894280
47. Overexpression of IMPACT in mouse embryonic fibroblasts inhibited phosphorylation of eIF2alpha by GCN2. PMID: 15937339
48. Brain-specific inactivation of GCN2 impairs the aversive response of omnivores to otherwise nutritious foods of imbalanced amino acid content. PMID: 16054071
49. genetic, physiological, behavioural and molecular evidence that GCN2 regulates synaptic plasticity, as well as learning and memory, through modulation of the ATF4/CREB pathway PMID: 16121183
50. functions to cooperatively regulate eIF2alpha phosphorylation and cyclin D1 translation after unfolded response pathway activation. PMID: 16176978

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KEGG: mmu:27103

STRING: 10090.ENSMUSP00000005233

UniGene: Mm.217616