ライフサイエンスコーパス: DGK

1 DGK activity was increased in lysates of insect cells in

2 DGK inhibition resulted in a dramatic reduction of cellu

3 DGK inhibitor R59949 injected into the vitreous dose dep

4 DGK zeta also coimmunoprecipitated and colocalized with

5 DGK zeta also coimmunoprecipitated with PKC alpha, sugge

6 DGK zeta, but not other DGKs, completely eliminated Ras

7 DGK-1, like DGK, has three cysteine-rich domains (CRDs),

8 DGK-1, the Caenorhabditis elegans ortholog of human neur

9 DGK-alpha inhibition and provision of IL-2 signals could

10 DGKs regulate Ras signaling by attenuating the function

11 , were upregulated in anergic T cells, and a DGK inhibitor restored interleukin 2 production in anerg

12 otein levels were significantly reduced by a DGK inhibitor, but tyrosinase and microphthalmia-associa

13 yltrimethylammonium chloride, also activated DGK alpha.

14 E (VtE) ameliorates DN in rat by activating DGK, and we recently reported that VtE specifically acti

15 These retinal hemodynamic parameters after DGK inhibition were comparable to those measured at base

16 ayed from five nondiabetic rat retinas after DGK inhibition and retinal PKC activities were assayed f

17 ey residues required for the function of all DGKs.

18 r, we show that diacylglycerol kinase alpha (DGK-alpha), which phosphorylates diacylglycerol to phosp

19 Diacylglycerol kinase-alpha (DGK-alpha) was more highly expressed in CD8-TILs compare

20 , which include loss of the GOA-1 G(o)alpha, DGK-1 diacylglycerol kinase, EAT-16 G protein gamma subu

21 Although DGK activity is known to be involved in plant developmen

22 Heterogeneity among DGK family members indicates that individual DGKs may ha

23 Both anergy and DGK-alpha overexpression were associated with defective

24 OGPOGPO-NH2, substituting KGE, KGD, EGK, and DGK for the YGX sequence.

25 In contrast, GOA-1 (Goalpha) and DGK-1 (diacylglycerol kinase) appear to negatively regul

26 The Rac-associated PtdInsP 5-kinase and DGK copurify by liquid chromatography, suggesting that t

27 ng clear that PA generated via the LPAAT and DGK pathways is also involved in the regulation of mTOR.

28 While inhibition of both PLD and DGK had no effect on the overall ERK activity, inhibitio

29 hat PA was generated sequentially by PLD and DGK in epidermal growth factor (EGF)-stimulated HCC1806

30 ospholipid biosynthesis, whereas the PLD and DGK pathways are activated in response to growth factors

31 inated Ras activation induced by RasGRP, and DGK activity was required for this mechanism.

32 re mediated by GOA-1 (a Galpha0 subunit) and DGK-1 (a diacylglycerol [DAG] kinase), both of which act

33 cent IIC9 cells indicates that DGK-theta and DGK-delta are both present.

34 In addition, a monoclonal anti-DGK-theta antibody inhibited the alpha-thrombin-stimulat

35 ty requires recruitment of the beta-arrestin-DGK complex to activated 7TMRs.

36 ylating the MARCKS PSD, PKC alpha attenuates DGK zeta activity.

37 ssment of the intricate interactions between DGK and ENaC and is consistent with available literature

38 tant for the termination of DAG signaling by DGK-1 in vivo.

39 during symbiosis establishment, mediated by DGKs, are required for the mutualistic outcome of the Rh

40 study, we demonstrate that DAG metabolism by DGKs can serve a crucial function in viral clearance upo

41 DAG analogues that cannot be metabolized by DGKs, suggesting that DAG signaling can induce their int

42 tenuate local accumulation of signaling DAG, DGKs may regulate RasGRP activity and, consequently, act

43 Finally, overexpression of kinase-dead DGK zeta in Jurkat cells prolonged Ras activation after

44 Furthermore, decreased DGK activity also promotes thymic lymphomagenesis accomp

45 1 metabotropic glutamate receptor-dependent DGK activity combined with a loss of Dgkkappa expression

46 se interested in the structure of eukaryotic DGKs, so that they know which expression strategies have

47 ur data support a causal function for excess DGK activity and defective Ras signaling in T cell anerg

48 porting this, we found that cells expressing DGK zeta S/D had higher DAG levels and grew more rapidly

49 more rapidly compared with cells expressing DGK zeta S/N that could not be phosphorylated.

50 domains that are thought to be important for DGK function including the cysteine-rich motifs and pote

51 lerance to amino acid substitutions seen for DGK and other membrane proteins.

52 iating this effect, we knocked down all four DGK isoforms expressed in the brain (beta, gamma, epsilo

53 nd the decrease of tyrosinase resulting from DGK inhibition could be blocked partially by protease in

54 K and in the rdgA mutant, lacking functional DGK, implicating DGK.

55 We generated DGK-alpha-deficient mice and found that DGK-alpha-defici

56 otein that is significantly similar to human DGK-theta, DGKA, was identified in Dictyostelium discoid

57 amino acid residues are present in all human DGKs and likely define key residues required for the fun

58 To identify DGK domains and amino acid residues critical for termina

59 mutant, lacking functional DGK, implicating DGK.

60 ological inhibition of DGK-alpha activity in DGK-zeta-deficient T cells that received an anergizing s

61 o, we analyzed 20 dgk-1 mutants defective in DGK-1-controlled behaviors.

62 In vivo anergy induction was impaired in DGK-alpha-deficient mice.

63 LXXLL motifs in DGK-theta mediate a direct interaction of SF1 with the k

64 MARCKS) phosphorylation site domain (PSD) in DGK zeta was phosphorylated in vitro by an active fragme

65 DGK family members indicates that individual DGKs may have unique functions.

66 t as a functional unit during Ca(2+)-induced DGK alpha activation.

67 The ATP effect was abolished by inhibiting DGK and in the rdgA mutant, lacking functional DGK, impl

68 bservations that phosphatidylserine inhibits DGK-delta, and constitutively active RhoA inhibits DGK-t

69 lta, and constitutively active RhoA inhibits DGK-theta to identify the activity induced by alpha-thro

70 Thus, type IV DGKs regulate RasGRPs, but the downstream effects differ

71 Diacylglycerol kinase alpha is an 82-kDa DGK isoform that is activated in vitro by Ca(2+).

72 DAG kinase (DGK) terminates DAG signaling by converting it to phosph

73 cent studies of diacylglycerol (DAG) kinase (DGK) 5, an enzyme involved in PA biosynthesis, facilitat

74 and silenced by ATP, suggesting DAG-kinase (DGK) involvement.

75 dly increases nuclear diacylglycerol kinase (DGK) activity and PA production.

76 Diacylglycerol kinase (DGK) activity was important for these lipid metabolic ch

77 ey anergy target gene diacylglycerol kinase (DGK) alpha as a focal point, we identified early growth

78 ull-length Sus scrofa diacylglycerol kinase (DGK) alpha or the catalytic domain (alphacat) in Escheri

79 Diacylglycerol kinase (DGK) catalyzes the conversion of diacylglycerol to phosp

80 racellular signaling; diacylglycerol kinase (DGK) catalyzes the phosphorylation of DAG, which yields

81 Diacylglycerol kinase (DGK) converts DG into phosphatidic acid.

82 activation of PKC and diacylglycerol kinase (DGK) coupled with upregulation of MAPK (mitogen-activate

83 The diacylglycerol kinase (DGK) family of enzymes plays critical roles in lipid sig

84 Diacylglycerol kinase (DGK) from Escherichia coli contains three transmembrane

85 gral membrane protein diacylglycerol kinase (DGK) from Escherichia coli has been reversibly unfolded

86 eric membrane protein diacylglycerol kinase (DGK) from Escherichia coli.

87 We found that diacylglycerol kinase (DGK) inhibitor II (R59949) decreased caspase-3/7 activit

88 l blood flow studies, diacylglycerol kinase (DGK) inhibitor R59949, at various concentrations, was in

89 Diacylglycerol kinase (DGK) phosphorylates diacylglycerol (DAG) to generate pho

90 Diacylglycerol kinase (DGK) plays a key role in cellular processes by regulatin

91 Diacylglycerol kinase (DGK) produces PA by phosphorylating diacylglycerol, a cr

92 Diacylglycerol kinase (DGK) terminates diacylglycerol (DAG) signaling by phosph

93 e identification of a diacylglycerol kinase (DGK) which also associates with both GTP- and GDP-bound

94 Inhibition of diacylglycerol kinase (DGK), an enzyme of the phosphoinositide pathway, reduces

95 n to this problem for diacylglycerol kinase (DGK), an integral membrane protein from Escherichia coli

96 hospholipase D (PLD), diacylglycerol kinase (DGK), and lysophosphatidic acid acyltransferase (LPAAT).

97 D (PLD1 and PLD2) or diacylglycerol kinase (DGK), two enzyme classes involved in PA production.

98 acterized the role of diacylglycerol kinase (DGK), which phosphorylates DAG to generate phosphatidic

99 ic acid, catalyzed by diacylglycerol kinase (DGK).

100 which is catalyzed by diacylglycerol kinase (DGK).

101 pholipase D (PLD) and diacylglycerol kinase (DGK).

102 Diacylglycerol kinase (DGK)zeta is a negative regulator of diacylglycerol-depen

103 t genetic deletion of diacylglycerol kinase (DGK)zeta, a negative regulator of diacylglycerol-mediate

104 We demonstrated further that DAG kinases (DGKs) alpha and zeta, which terminate DAG-mediated signa

105 DAG kinases (DGKs) convert DAG into phosphatidic acid, resulting in t

106 cerol (DAG) and the activity of DAG kinases (DGKs) in membranous structures.

107 DAG kinases (DGKs) metabolize DAG by converting it to phosphatidic ac

108 PLC) enzymes and termination by DAG kinases (DGKs), as well as dysregulation in the activity or abund

109 Diacylglycerol (DAG) kinases (DGKs) are a family of enzymes that convert DAG to phosph

110 Diacylglycerol (DAG) kinases (DGKs) regulate the intracellular levels of two important

111 Diacylglycerol kinases (DGKs) attenuate diacylglycerol (DAG) signaling by conver

112 Diacylglycerol kinases (DGKs) catalyze the ATP-dependent phosphorylation of diac

113 We show that diacylglycerol kinases (DGKs) DGK1 and DGK2 form a module with SYT1 functionally

114 Diacylglycerol kinases (DGKs) inhibit diacylglycerol (DAG) signaling by phosphor

115 Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol (DAG) to terminate it

116 Diacylglycerol kinases (DGKs) phosphorylate diacylglycerol produced during stimu

117 Diacylglycerol kinases (DGKs) terminate signalling from diacylglycerol by conver

118 ically interact with diacylglycerol kinases (DGKs), enzymes that degrade DAG.

119 tightly regulated by diacylglycerol kinases (DGKs), is a lipid mediator linked to key biologic functi

120 ergy, we manipulated diacylglycerol kinases (DGKs), which are enzymes that terminate diacylglycerol-d

121 Diacylglycerol kinases (DGKs), which negatively regulate Ras activity, were upre

122 matic degradation by diacylglycerol kinases (DGKs).

123 ible cDNA with substantial homology to known DGKs.

124 anergy-producing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleu

125 In the present study, we tested full-length DGK zeta and found that PKC alpha phosphorylated DGK zet

126 DGK-1, like DGK, has three cysteine-rich domains (CRDs), a pleckstri

127 We found that a mutant (DGK zeta S/D) in which serines within the MARCKS PSD wer

128 with wild-type DGK zeta or a control mutant (DGK zeta S/N) in which the same serines were changed to

129 rhabditis elegans ortholog of human neuronal DGK, inhibits neurotransmission to control behavior.

130 the activity of wild-type DGK zeta, but not DGK zeta S/D, in human embryonic kidney 293 cells.

131 We isolated a novel DGK, which we designated DGKiota, from human retina and

132 ibroblasts results in an increase in nuclear DGK activity.

133 trate an agonist-induced activity of nuclear DGK-theta activity and a nuclear localization of DGK-del

134 efore, it is expected that the activation of DGK would ameliorate DN.

135 facial association and catalytic activity of DGK-theta are independently regulated.

136 little effect on the membrane association of DGK-theta, suggesting that a triad of enzyme, acidic lip

137 s form a previously uncharacterized clade of DGK domain proteins.

138 Coimmunoprecipitation of DGK zeta and RasGRP was enhanced in the presence of phor

139 Thus, precise control of DGK activity is essential for proper signal transduction

140 ing distinct temporal and spatial control of DGK activity to each isozyme.

141 es may serve as the messengers downstream of DGK and PLA2, respectively.

142 onstrate that generation of PA downstream of DGK-alpha is essential to connect expression of mutant p

143 eral T cells abolishes induced expression of DGK-alpha and other anergy genes and restores Ras/MAPK s

144 glycerol levels by conditional expression of DGK-zeta attenuates cell growth.

145 Here we show that a fraction of DGK-zeta is found in the nucleus, where it regulates the

146 s that impair the physiological functions of DGK-1.

147 n in mast cells and reveal the importance of DGK activity during IgE sensitization for proper attenua

148 Inhibition of DGK activity attenuates the binding of SF1 to the CYP17

149 of the PA production, whereas inhibition of DGK decreased PA production only at the later stages of

150 Pharmacological inhibition of DGK diminished both airway inflammation and AHR in mice

151 sidase digestion revealed that inhibition of DGK reduced only the mature form of tyrosinase, and the

152 Pharmacological inhibition of DGK-alpha activity in DGK-zeta-deficient T cells that re

153 mice, we determined that the zeta isoform of DGK (DGKzeta) is necessary for the mechanically induced

154 Ten isoforms of DGK have been identified, and we show that DGKzeta is th

155 theta activity and a nuclear localization of DGK-delta.

156 but not others, regulate the localization of DGK-zeta.

157 by alternating the intracellular location of DGK-zeta.

158 ous application of phorbol esters or loss of DGK-1 (diacylglycerol kinase) rescues ric-8 mutant pheno

159 into TM1 and flanking sites, in a mutant of DGK lacking the two native Cys residues.

160 xpression of a constitutive-active mutant of DGK-alpha drove RCP-dependent invasion in the absence of

161 Twelve enhanced stability mutants of DGK were obtained using a simple screen.

162 Overexpression of DGK-alpha resulted in a defect in T cell receptor signal

163 monstrate a synergistic and critical role of DGK isoforms in T cell development and tumor suppression

164 Ca(2+) regulation, we expressed a series of DGK alpha deletions spanning its regulatory domain in CO

165 The nuclear-localization signal of DGK-zeta is located in a region that is homologous to th

166 SF1 to the CYP17 promoter, and silencing of DGK-theta expression inhibits cAMP-dependent CYP17 trans

167 alpha-thrombin induced the translocation of DGK-theta to the nucleus, implicating that this transloc

168 A complete understanding of DGK catalytic and regulatory mechanisms, as well as phys

169 A family of DGKs has been identified in multicellular organisms over

170 ing conditions, T cells lacking DGK-alpha or DGK-zeta proliferated and produced interleukin 2.

171 activity, inhibition of PLD2 but not PLD1 or DGK blocked the nuclear ERK activity in several cancer c

172 noblots) was broader than reported for other DGKs, indicating that DGKeta may play a more general rol

173 DGK zeta, but not other DGKs, completely eliminated Ras activation induced by Ra

174 in regulating cellular DG levels than other DGKs.

175 Homology to other DGKs was apparent in domains that are thought to be impo

176 zeta and found that PKC alpha phosphorylated DGK zeta on serines within the MARCKS PSD in vitro and i

177 sults indicate that PKC alpha phosphorylates DGK zeta in cells, and this phosphorylation inhibits its

178 It has been shown to possess DGK activity when assayed using a medium-chain diacylgly

179 F stimulation, suggesting that PLD2 precedes DGK activation.

180 exons containing the stop codons to produce DGK-1 isoforms that contain the kinase domain.

181 Using purified DGK-theta, we show that this isoform is subject to dual

182 he phenyl-Sepharose binding of a recombinant DGK alpha fragment that included both the RVH domain and

183 Cultivation of TILs in low-dose IL-2 reduced DGK-alpha protein levels, increased steady-state phospho

184 h comprehensive transcriptomic data of seven DGKs and genetic crossing, we found that dgk2-1/- dgk4-1

185 evelopment and stress response, how specific DGK isoforms function in development and phospholipid me

186 phobic core of the lipid bilayer surrounding DGK in reconstituted membranes.

187 Ten DGK family isozymes have been identified to date, which

188 DGKzeta inhibits PKCalpha activity and that DGK activity is required for this inhibition.

189 tively regulates the EGL-30 pathway and that DGK-1 antagonizes the EGL-30 pathway.

190 These results demonstrate that DGK-theta is the isoform responsive to alpha-thrombin st

191 ated DGK-alpha-deficient mice and found that DGK-alpha-deficient T cells had more diacylglycerol-depe

192 We report here that DGK alpha and zeta synergistically promote T cell matura

193 ted from quiescent IIC9 cells indicates that DGK-theta and DGK-delta are both present.

194 Finally, we show that DGK-theta directly interacts with, and is activated by,

195 In contrast to previous studies showing that DGK isoforms decrease Ras activity, signaling downstream

196 These data suggest that DGK is a previously unrecognized therapeutic target for

197 These results suggest that DGK regulates melanogenesis via modulation of the posttr

198 ent and tumor suppression, and indicate that DGKs not only terminate DAG signaling but also initiate

199 The DGK alpha regulatory region includes tandem C1 protein k

200 the products of the PtdInsP 5-kinase and the DGK have been implicated in several Rac-regulated proces

201 GK peptide has lower thermostability and the DGK peptide is the least thermostable.

202 We identify the DGK-3 diacylglycerol kinase as a thermal memory molecule

203 KGE and KGD sequences, and the least in the DGK sequence.

204 expression of OsDGK1 led to a decline in the DGK substrate DAG whereas specific PA species decreased

205 We demonstrate that the zeta isoform of the DGK family (DGKzeta) is expressed in macrophages (Mphi)

206 s sequence appears to be a new member of the DGK family that we refer to as DGKeta.

207 Members of the DGK family undergo alternative splicing, generating the

208 y phosphatidic acid (PA), the product of the DGK reaction.

209 onal novel isoform(s) account for all of the DGK-1 function necessary for one behavior, dopamine resp

210 e downstream effects differ depending on the DGK.

211 dition, treatment of rice seedlings with the DGK inhibitor R59022 increased the level of DAG and decr

212 Lastly, our study revealed that the DGKs involved in the symbiosis form a previously unchara

213 ovel way to regulate Ras activation: through DGK zeta, which controls local accumulation of DAG that

214 Thus, DGK activity plays opposing roles in the expansion of CD

215 two stop codon mutants predicted to truncate DGK-1 before its kinase domain that retained significant

216 Two DGK family members, delta and eta, contain a sterile alp

217 In n-octylglucoside, the wild-type DGK had a thermal inactivation half-life of 6 min at 55

218 ) had lower activity compared with wild-type DGK zeta or a control mutant (DGK zeta S/N) in which the

219 -acetate inhibited the activity of wild-type DGK zeta, but not DGK zeta S/D, in human embryonic kidne

220 ernalization and CCP dynamics, compared with DGK inhibition.

221 ocytic choriomeningitis virus infection, yet DGK-deficient memory CD8(+) T cells exhibit impaired exp