ライフサイエンスコーパス: eIF2alpha kinase

1 ssing the mammalian tumor suppressor PKR, an eIF2alpha kinase.

2 s have been attributed to its function as an eIF2alpha kinase.

3 ), the double-stranded RNA (dsRNA)-dependent eIF2alpha kinase.

4 d through the general control nonrepressed-2 eIF2alpha kinase.

5 otic initiation factor 2alpha (eIF2alpha) by eIF2alpha kinases.

6 human PKR and yeast GCN2, which are defined eIF2alpha kinases.

7 ition site capability similar to established eIF2alpha kinases.

8 n, was found to inhibit both human and yeast eIF2alpha kinases.

9 the antiviral protein kinase PKR and related eIF2alpha kinases.

10 re is critical for the activity of all three eIF2alpha kinases.

11 a pseudosubstrate mechanism of inhibition of eIF2alpha kinases.

12 tivated eukaryotic initiation factor 2alpha (eIF2alpha) kinase.

13 HRI is the only eIF2alpha kinase activated by arsenite in erythroid cell

14 The primary eIF2alpha kinase activated by exposure of these fibrobla

15 The in vitro autophosphorylation and eIF2alpha kinase activities of the dephosphorylated enzy

16 al junction of dsRBD2 dramatically increased eIF2alpha kinase activity and characterization of larger

17 d in reduced autokinase activity and loss of eIF2alpha kinase activity in heme deficiency or upon ars

18 ssary for arsenite-induced activation of the eIF2alpha kinase activity of HRI, while autophosphorylat

19 but not Thr483, was essential for attaining eIF2alpha kinase activity of HRI.

20 autophosphorylation reaction stimulates the eIF2alpha kinase activity of PKR.

21 tion of stable dimeric HRI (species II) with eIF2alpha kinase activity that is regulated by heme.

22 is an active autokinase, it is still without eIF2alpha kinase activity.

23 eletion of dsRBD1 severely reduced the basal eIF2alpha kinase activity.

24 I and is required for the acquisition of the eIF2alpha kinase activity.

25 major role in defense against viruses, other eIF2alpha kinases also may respond to viral infection an

26 gly, these two residues are conserved in all eIF2alpha kinases, although in the GCN2 structure, the t

27 ated species II was an active heme-regulated eIF2alpha kinase and stable homodimer.

28 turally distinct effectors of eIF2 function, eIF2alpha kinases and eIF2B, have evolved to recognize t

29 ication is more efficient in the presence of eIF2alpha kinases and phosphorylatable eIF2alpha.

30 ology among eukaryotic eIF2alpha species and eIF2alpha kinases and support the presence of a plant eI

31 like endoplasmic reticulum kinase/pancreatic eIF2alpha kinase, and that activation of these kinases i

32 the substrate recognition properties of the eIF2alpha kinases, and they are intriguing considering t

33 The eIF2alpha kinases are a family of evolutionarily conserv

34 unique to vertebrates and suggest that these eIF2alpha kinases are important participants in diverse

35 We conclude that eIF2alpha kinases are integral to cellular stress pathwa

36 We propose that this eIF2alpha-kinase/ATF4/C/EBP-ATF composite site pathway i

37 Here we report the inhibition of a second eIF2alpha kinase by E2, and these results are consistent

38 Therefore, we tested whether suppressing eIF2alpha kinases could alleviate synaptic plasticity an

39 tic function provides an explanation for why eIF2alpha kinase deficiency in diseases such as Wolcott-

40 r hPKR or pPKR suggesting that this putative eIF2alpha kinase docking domain is essential for phospho

41 structure represents the active state of the eIF2alpha kinase domain, whereas the GCN2 structure may

42 Overexpression of Hri1p, Hri2p, or the human eIF2alpha kinase, double-stranded-RNA-dependent protein

43 irus, suggesting an IFN-independent role for eIF2alpha kinases during infection.

44 Central to this pro-apoptotic function of eIF2alpha kinases during proteasome inhibition is the tr

45 manner, but not the heme-regulated inhibitor eIF2alpha kinase [(EIF2AK1)].

46 ain residues preferentially conserved in the eIF2alpha kinase family identifies helix alphaG as criti

47 One member of the eIF2alpha kinase family, heme-regulated inhibitor kinase

48 umor microenvironment, activation of diverse eIF2alpha kinases followed by IFNAR1 downregulation enab

49 umor microenvironment, activation of diverse eIF2alpha kinases followed by IFNAR1 downregulation enab

50 n the activation loop and stimulation of the eIF2alpha kinase function of PKR.

51 A family of different eIF2alpha kinases function in the integrative stress res

52 s of cyclin D1 loss, suggesting that another eIF2alpha kinase functions in the absence of PERK.

53 The activity of this artificial eIF2alpha kinase, Fv2E-PERK, is subordinate to the dimer

54 We found that the yeast eIF2alpha kinase GCN2 autophosphorylates at Thr-882 and

55 translation, by stimulating the function of eIF2alpha kinase Gcn2 during histidine starvation of glu

56 subunit of translation initiation factor 2 (eIF2alpha) kinase GCN2 and consequent induction of GCN4,

57 pstream eukaryotic initiation factor 2alpha (eIF2alpha) kinase GCN2 to upregulate ATF4 target genes i

58 ble the activation of the amino acid-sensing eIF2alpha kinase, Gcn2, and to promote autophagy.

59 howed that this pathway was activated by the eIF2alpha kinase, GCN2, in an apparent deacylated tRNA-i

60 Similarly, deletion of another eIF2alpha kinase, GCN2, prevented impairments of synapti

61 Here, we demonstrate that the yeast eIF2alpha kinase, GCN2, the target phosphorylation site

62 unction eukaryotic initiation factor-2alpha (eIF2alpha) kinase (Gcn2p) mutation permitted growth duri

63 vation of a stress response dependent on the eIF2alpha kinase general control nonderepressible 2 (GCN

64 GF21 levels were reduced in mice lacking the eIF2alpha kinase general control nonderepressible 2 (GCN

65 promotes tryptophan depletion, activates the eIF2alpha kinase general control nonderepressible-2 (GCN

66 kinase subdomain V, which is conserved among eIF2alpha kinases, has been proposed to determine substr

67 te in PKR binding, pTRS1 bound an additional eIF2alpha kinase, heme-regulated inhibitor (HRI), and in

68 Heme-regulated eIF2alpha kinase (HRI) controls protein synthesis by pho

69 hibited the maturation of the heme-regulated eIF2alpha kinase (HRI) in a concentration-dependent mann

70 tion of the gene encoding the heme-regulated eIF2alpha kinase (HRI) in mice.

71 (CO) on the activation of the heme-regulated eIF2alpha kinase (HRI) in rabbit reticulocyte lysate.

72 Heme-regulated eIF2alpha kinase (HRI) is a key hemoprotein in erythroid

73 Heme-regulated eIF2alpha kinase (Hri) is necessary for balanced synthes

74 Heme-regulated eIF2alpha kinase (HRI) plays an essential protective rol

75 ited by the activation of the heme-regulated eIF2alpha kinase (HRI) through its multiple autophosphor

76 ited due to the activation of heme-regulated eIF2alpha kinase (HRI).

77 ISR) during erythropoiesis by heme-regulated eIF2alpha kinase (HRI).

78 n Hsp90-dependent kinase, the heme-regulated eIF2alpha kinase (HRI).

79 tyrosine kinase, Lck, and the heme-regulated eIF2alpha kinase (HRI)], and the association of Hsp90 an

80 ryotic translation initiation factor 2alpha (eIF2alpha) kinase (HRI).

81 Specifically, strains lacking the eIF2alpha kinase Hri2 were particularly sensitive to Ypk

82 otozoan that causes malaria, expresses three eIF2alpha kinases: IK1, IK2, and PK4.

83 ed by a eukaryotic initiation factor-2alpha (eIF2alpha) kinase (IK2) and a phosphatase.

84 eneral control nonderepressible-2 (EIF2AK4)] eIF2alpha kinase in a concentration-dependent manner, bu

85 e broadly utilized by stresses that activate eIF2alpha kinases in order to coordinately regulate tran

86 ons in murine cells reveals a novel role for eIF2alpha kinases in regulating gene expression in the u

87 -regulated inhibitor (HRI), a heme-regulated eIF2alpha kinase, in stress responses of erythroid cells

88 The GCN2 eIF2alpha kinase is essential for activation of the gene

89 MRV induced SG formation in all four eIF2alpha kinase knockout cell lines, suggesting that at

90 portant for YpkA activity and found that the eIF2alpha kinases mollify the toxicity imparted by the k

91 Together, these studies suggest that eIF2alpha kinases monitor and are activated by a range o

92 lly elevated, or dependent on Gcn2, the sole eIF2alpha kinase of yeast, in histidine-deprived cells.

93 human protein kinase RNA-regulated (PKR), an eIF2alpha kinase, on virus production was counteracted b

94 By contrast, inhibition of an eIF2alpha kinase or blocking the translational program c

95 creatic eukaryotic initiation factor 2alpha (eIF2alpha) kinase or PKR (double-stranded RNA-activated

96 vel evolutionarily conserved function of the eIF2alpha kinase pathway that is targeted by viral virul

97 ctivation of the ER stress sensory proteins, eIF2alpha kinase PEK (PERK/EIF2AK3), IRE1 protein kinase

98 ng the gene encoding the ER stress-activated eIF2alpha kinase PERK abolishes the phosphorylation of e

99 Genetic deletion of eIF2alpha kinase PERK prevented enhanced phosphorylation

100 The endoplasmic reticulum (ER)-resident eIF2alpha kinase PERK was hyperphosphorylated upon hypox

101 e PP1c regulatory subunit, dominant-negative eIF2alpha kinase PERK, or PERK inhibitor P58(IPK) blocks

102 -1, the C. elegans ortholog of the mammalian eIF2alpha kinase PERK, which in turn phosphorylates Ser4

103 with and inhibits the PKR-like ER-localized eIF2alpha kinase PERK, which is normally activated durin

104 HCMV infection activated the eIF2alpha kinase PERK; however, the amount of phosphoryl

105 mal activity of the cognate stress-inducible eIF2alpha kinases PERK (also known as PEK) and GCN2, pho

106 an target of rapamycin (mTOR) and pancreatic eIF2alpha kinase (PERK) pathways.

107 tein response, IRE1alpha, ATF6, and PKR-like eIF2alpha kinase (PERK), significantly decreased both au

108 istinct stress conditions activate different eIF2alpha kinases (PERK, PKR, GCN2, and HRI) that conver

109 ryotic translation initiation factor 2alpha (eIF2alpha) kinase (PERK).

110 Activation of the ER transmembrane eIF2alpha kinase, PERK, induced ATF4 protein expression,

111 ion of the PKR-related endoplasmic reticulum eIF2alpha kinase, PERK.

112 hosphorylation is mediated by the Plasmodium eIF2alpha kinase, PK4.

113 eron-induced, double-stranded RNA-responsive eIF2alpha kinase PKR, and it does not require either the

114 ation of eIF2alpha and the activation of the eIF2alpha kinase PKR.

115 pase 3 primarily through the dsRNA-activated eIF2alpha kinase PKR.

116 of the eukaryotic initiation factor 2alpha (eIF2alpha) kinases PKR and PERK.

117 The mammalian IFN-inducible eIF2alpha kinase, PKR, rescues starvation-induced autoph

118 ase domain most similar to that of the known eIF2alpha kinases, PKR and HRI.

119 n, we pharmacologically inhibited one of the eIF2alpha kinases, PKR, which is known to be involved in

120 yotic translation initiation factor 2 alpha (eIF2alpha) kinase, plays critical roles in cell prolifer

121 ced phosphorylation of eIF2alpha through the eIF2alpha kinase protein kinase R (PKR).

122 HRI is also the major eIF2alpha kinase responsible for the increased eIF2alpha

123 Activators of other eIF2alpha kinases such as PKR or GCN2 (general control n

124 8(IPK) to interact with and inhibit multiple eIF2alpha kinases suggests it is a critical regulator of

125 lls, lacking an upstream ER stress-activated eIF2alpha kinase that activates Atf4, accumulate endogen

126 P58(IPK) also inhibits PERK, an eIF2alpha kinase that is localized in the endoplasmic re

127 iculum kinase (PERK), an ER stress-inducible eIF2alpha kinase that is normally activated by dimerizat

128 achieved by activation of a PERK-independent eIF2alpha kinase through arsenite treatment and is indep

129 tic ER kinase (PERK, an ER stress-responsive eIF2alpha kinase) to uncouple eIF2alpha phosphorylation

130 karyotic initiation factor phosphorylated by eIF2alpha kinases under stress conditions.

131 st, the substrate specificity of these three eIF2alpha kinases was examined by substituting Ser-51 in

132 sights into the substrate specificity of the eIF2alpha kinases, we have determined the nuclear magnet

133 ividual eukaryotic initiation factor 2alpha (eIF2alpha) kinases, we identified protein kinase R as th

134 tionally link YpkA and YopJ and suggest that eIF2alpha kinases, which are critically important in ant