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 d through the general control nonrepressed-2 eIF2alpha kinase.

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

5 a pseudosubstrate mechanism of inhibition of eIF2alpha kinases.

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

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

8 ition site capability similar to established eIF2alpha kinases.

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

10 cells, including RPLP0/uL10 levels, activate eIF2alpha kinases.

11 aling pathways initiated by stress-activated eIF2alpha kinases.

12 the antiviral protein kinase PKR and related eIF2alpha kinases.

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

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

15 ation of eIF2alpha, surprisingly mediated by eIF2alpha kinase 1, or heme-regulated kinase inhibitor (

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

17 The primary eIF2alpha kinase activated by exposure of these fibrobla

18 idyl-tRNA synthetase-like domain of Gcn2 for eIF2alpha kinase activation by ribosomes stalled with A

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

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

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

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

23 here it interacts with HRI and activates the eIF2alpha kinase activity of HRI.

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

25 autophosphorylation reaction stimulates the eIF2alpha kinase activity of PKR.

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

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

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

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

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

31 Heme-regulated eIF2alpha kinase, also known as heme-regulated inhibitor

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

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

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

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

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

37 ased phosphorylation of eIF2alpha (Ser51) by eIF2alpha kinase, and of GCN-2 (general controlled non-d

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

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

40 The eIF2alpha kinases are a family of evolutionarily conserv

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

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

43 In addition to eIF2alpha kinases, ATF4 induction requires other regulat

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

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

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

47 a levels required rhythmic activation of the eIF2alpha kinase CPC-3 (the homolog of yeast and mammali

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

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

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

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

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

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

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

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

56 egulation is a universal hallmark across the eIF2alpha kinase family under various stress conditions

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

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

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

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

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

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

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

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

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

66 The eIF2alpha kinase GCN2 rhythmically phosphorylates eIF2al

67 letes asparagine, activating the ISR via the eIF2alpha kinase GCN2.

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

69 ryotic translation initiation factor 2alpha (eIF2alpha) kinase GCN2 is activated by amino acid starva

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

71 2) in ASCT2ko 143B cells, mediated by a GCN2 EIF2alpha kinase (GCN2)-dependent pathway, but this comp

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

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

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

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

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

77 The eIF2alpha kinase general control nonderepressible 2 (GCN

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

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

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

81 endoplasmic reticulum kinase (the canonical EIF2alpha kinase) had no effect.

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

83 We found that the eIF2alpha kinase heme-regulated inhibitor (HRI) controls

84 -globin gene requires the erythroid-specific eIF2alpha kinase heme-regulated inhibitor (HRI), suggest

85 Recently, we found that the eIF2alpha kinase heme-regulated inhibitory (HRI) induced

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

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

88 Heme-regulated eIF2alpha kinase (HRI) controls translation by phosphory

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

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

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

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

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

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

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

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

97 lpha (eIF2alpha) by DELE1 and heme-regulated eIF2alpha kinase (HRI).

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

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

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

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

102 ts of the regulated genes include additional eIF2alpha kinase Hri2 amplifying the stress signaling an

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

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

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

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

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

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

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

110 tions of eIF2alpha kinases or treatment with eIF2alpha kinase inhibitors being protective in some ani

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

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

113 , RAFi exposure activated GCN2, an alternate eIF2alpha kinase, leading to eIF2alpha-dependent (and ER

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

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

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

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

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

119 factor 2alpha (eIF2alpha), with deletions of eIF2alpha kinases or treatment with eIF2alpha kinase inh

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

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

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

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

124 Genetic deletion of eIF2alpha kinase PERK prevented enhanced phosphorylation

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

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

127 -1, the C. elegans ortholog of the mammalian eIF2alpha kinase PERK, which in turn phosphorylates Ser4

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

129 stress-induced ISR, mediated by the related eIF2alpha kinase PERK.

130 r defects upon overexpression of ATF4 or the eIF2alpha kinase PERK.

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

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

133 stress response (ISR) - comprising the four eIF2alpha kinases PERK, GCN2, PKR, and HRI - is a promin

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

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

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

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

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

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

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

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

142 We found that inhibition of the eIF2alpha kinase PKR-like ER kinase (PERK), a common com

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

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

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

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

147 Our results also indicate that of the two eIF2alpha kinases, PKR and GCN2, GCN2 is the primary ind

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

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

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

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

152 Two eukaryotic initiation factor 2alpha (eIF2alpha) kinases, protein kinase R (PKR) and general c

153 Distinct eIF2alpha kinases respond to different stress signals, i

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

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

156 8(IPK) to interact with and inhibit multiple eIF2alpha kinases suggests it is a critical regulator of

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

158 ffinity-regulating kinase 2 (MARK2) as a key eIF2alpha kinase that enhances RAN translation under pro

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

160 Here we show that HRI is the eIF2alpha kinase that is necessary and sufficient for th

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

162 stresses, in part, through stress activated eIF2alpha kinases that stimulate the translation of ATF4

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

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

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

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

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

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

169 sponse to dsRNA is the activation of PKR, an eIF2alpha kinase, which triggers translational arrest an

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