ライフサイエンスコーパス: PKC-beta

1 PKC beta (membrane only).

2 PKC beta and PKC gamma each bind three Ca(2+) ions in th

3 PKC beta and zeta downregulation served to promote diffe

4 PKC beta II activates the Cox-2 promoter by 2- to 3-fold

5 PKC beta recruitment to alpha(IIb)beta(3) was accompanie

6 PKC beta transfectant cells exhibited blocked differenti

7 PKC beta was not detected in lens or culture homogenates

8 PKC beta(I) and PKC beta(II), but not PKC alpha or PKC g

9 PKC-beta 2 was highly sensitive to downregulation, becau

10 PKC-beta contributes to hyperglycemia-induced renal matr

11 ssion plasmids for protein kinases C beta 1 (PKC beta 1) or PKC beta 2 into differentiated colon canc

12 expressed at equal abundance in PKC beta 1, PKC beta 2, and control transfectant cells as demonstrat

13 crease in epidermal protein kinase C-beta 2 (PKC-beta 2) compared with PKC-alpha as determined by wes

14 When PKC-alpha was decreased by 40%, PKC-beta 2 could no longer be detected, suggesting that

15 by intravitreal or oral administration of a PKC beta-isoform-selective inhibitor that did not inhibi

16 diabetic Sprague-Dawley rats (n = 33), and a PKC-beta isoform-selective inhibitor LY333531 was inject

17 Northern blot analysis revealed a PKC-beta 2 signal in isolated LCs that was 40-fold great

18 opment of diabetic macroangiopathy through a PKC-beta-ROS activation of JAK2.

19 Clinical trials using a PKC-beta isoform inhibitor have been conducted, with som

20 Transfecting HL-525 cells with a PKC-beta expression plasmid restored PKC-beta levels and

21 Transfecting HL-525 cells with a PKC-beta expression plasmid restored PMA-induced FN gene

22 isense oligonucleotide, preincubation with a PKC-beta-specific inhibitor (LY379196) or apocynin (NADP

23 ACK1, an intracellular adapter for activated PKC beta, also co-immunoprecipitated with alpha(IIb)beta

24 eraction of alpha(IIb)beta(3) with activated PKC beta is regulated by integrin occupancy and can be m

25 n of intact melanosomes with purified active PKC-beta in vitro increased tyrosinase activity 3-fold.

26 assayed from six diabetic rat retinas after PKC-beta inhibition.

27 expression of protein kinase C (PKC)-alpha, PKC-beta, protein oxidation, and nitrotyrosine in the sk

28 bol ester, which largely depletes PKC-alpha, PKC-beta, and PKC-epsilon, but not PKC-zeta.

29 PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon are foun

30 ribution of several PKC isoforms (PKC-alpha, PKC-beta, PKC-gamma, PKC-delta, and PKC-epsilon) within

31 lts suggest a translocation of PKC alpha and PKC beta from the cytosol to the membrane in the injured

32 ses in the levels of cytosolic PKC alpha and PKC beta in the injured cortex after brain injury.

33 le myenteric plexus content of PKC alpha and PKC beta is substantially elevated following chronic mor

34 ease in the levels of membrane PKC alpha and PKC beta was observed after injury.

35 discovered in retinal endothelial cells, and PKC beta 2 isoform increased retinoblastoma phosphorylat

36 by cellular PKC depletion and by general and PKC beta inhibition.

37 d selective for inhibition of PKC beta I and PKC beta II in comparison to PKC alpha, respectively.

38 Conversely, antisera to PKC beta(I) and PKC beta(II) but not PKC alpha or PKCg amma were able to

39 PKC beta(I) and PKC beta(II), but not PKC alpha or PKC gamma, were co-im

40 inhibits the PKC beta I (IC50 = 4.7 nM) and PKC beta II (IC50 = 5.9 nM) isozymes and was 76- and 61-

41 ing a functional association between PKK and PKC beta I.

42 vels of PKC beta 1 or PKC beta 2 protein and PKC beta kinase activities in the transfectants, without

43 eased expression/activation of PKC-alpha and PKC-beta and enhanced oxidative and nitrosative stress.

44 ts support our hypothesis that PKC-alpha and PKC-beta contribute to the pathogenesis of diabetic neph

45 clear membrane, in contrast to PKC-alpha and PKC-beta in the epidermal plasma membrane; (ii) that top

46 with CGP41252, which inhibits PKC-alpha and PKC-beta, is able to prevent the development of albuminu

47 nd Ca(2+) levels and activated PKC-alpha and PKC-beta-II.

48 ctivity and membrane levels of PKC-alpha and PKC-beta.

49 ional protein kinase C-alpha (PKC-alpha) and PKC-beta as important negative regulators of the RIG-I s

50 diators, and increased TRPC6, PKC-alpha, and PKC-beta expression.

51 to other known interacting proteins such as PKC beta and Src.

52 Membrane-associated PKC-beta protein was elevated under basal conditions, an

53 Protein levels of myofilament-associated PKC-beta were decreased in TG ventricle.

54 vation, and decreases myofilament-associated PKC-beta.

55 variant deficient in protein kinase C-beta (PKC-beta) and several stable PKC-beta transfectants, we

56 The role of protein kinase C-beta (PKC-beta) in apoptosis induced by tumor necrosis factor

57 ressed by a selective protein kinase C-beta (PKC-beta) inhibitor.

58 Protein kinase C-beta (PKC-beta) is immediately downstream of BCR and has been

59 previously shown that protein kinase C-beta (PKC-beta) is required for activation of tyrosinase, the

60 -alpha (cPLA2-alpha), protein kinase C-beta (PKC-beta), and synaptotagmin-IA (Syt-IA).

61 B cells from protein kinase C-beta (PKC-beta)-deficient mice failed to recruit the I kappa B

62 A causal link between PKC beta overexpression and ERK3 activation was establis

63 Blocking PKC beta translocation with hispidin resulted in more ra

64 Broad spectrum PKC inhibitors blocked both PKC beta recruitment to alpha(IIb)beta(3) and the spread

65 gulated both PKC and ERK3 activities in both PKC beta 1 transfectants.

66 In vitro phosphorylation of SAF-1 by PKC-beta markedly increased its DNA binding ability.

67 nase-phosphorylated in intact melanocytes by PKC-beta and then subjected to trypsin digestion reveale

68 in the retina are mediated in large part by PKC-beta.

69 t both serine residues are phosphorylated by PKC-beta.

70 ch is deficient in the protein kinase Cbeta (PKC-beta) and resistant to PMA-induced differentiation,

71 These results suggest that classical PKC beta(II) is physically associated with DAT and is im

72 r specific epidermal cell types that contain PKC-beta 2 are more sensitive to TPA/diacylglycerol.

73 5 cells with an expression vector containing PKC-beta reestablished their susceptibility to TNF-alpha

74 a C1A-C1B domain also activated conventional PKC beta I, -beta II, and -gamma isoforms, but not novel

75 Diabetic PKC-beta(-/-) mice were protected from renal hypertrophy

76 parameters of oxidative stress, in diabetic PKC-beta(-/-) mice were significantly reduced compared w

77 ntly reduced (<50% of wild-type) in diabetic PKC-beta(-/-) mice.

78 renal cortex and were unchanged in diabetic PKC-beta(-/-) mice.

79 ic wild-type mice was attenuated in diabetic PKC-beta(-/-) mice.

80 > 10-fold increase in ERK3 activity in each PKC beta transfectant was shown by immunoprecipitation w

81 nd in nuclear and membrane fractions in each PKC beta transfectant, in contrast to controls, perhaps

82 verexpress an exogenous PKC alpha or ectopic PKC beta 1 exhibited more marked growth inhibition by TP

83 ) but rather through induction of endogenous PKC-beta gene expression by the transfected classical PK

84 data indicate that (i) within the epidermis, PKC-beta 2 is highly sensitive to downregulation and is

85 or PKC gamma C2 domain (H = 2.3 +/- 0.1 for PKC beta, 0.9 +/- 0.1 for PKC alpha, and 0.9 +/- 0.1 for

86 ins (Hill coefficients equal 1.8 +/- 0.1 for PKC beta, 1.3 +/- 0.1 for PKC alpha, and 1.4 +/- 0.1 for

87 oM for PKC alpha, and 5.0 +/- 0.2 microM for PKC beta), and cooperative Ca(2+) binding is observed fo

88 characterization of a specific inhibitor for PKC-beta isoforms have confirmed the role of PKC activat

89 her, these data define an essential role for PKC-beta in BCR survival signaling and highlight PKC-bet

90 beta in BCR survival signaling and highlight PKC-beta as a key therapeutic target for B-lineage malig

91 ll interfering (si)RNAs but not by hispidin (PKC-beta inhibitor).

92 e evidence linking bacterial PI-PLC and host PKC beta to phagosome permeabilization, which precedes e

93 iated PKC activity was not changed; however, PKC-beta protein content, assayed by Western blot analys

94 ated expression of protein kinase C beta II (PKC beta II) is an early promotive event in colon carcin

95 ERK3 was expressed at equal abundance in PKC beta 1, PKC beta 2, and control transfectant cells a

96 Mice deficient in PKC beta showed normal brain anatomy and normal hippocam

97 platelets that are genetically deficient in PKC beta spread poorly on fibrinogen, despite normal ago

98 nt decrease in retinal neovascularization in PKC beta isoform null mice.

99 these cells, so the major modulation was in PKC beta.

100 ng its variant HL-525, which is deficient in PKC-beta.

101 rane, whereas only PKC-alpha was elevated in PKC-beta(-/-) mice.

102 normalize diabetes or hyperglycemia-induced PKC beta-isoform activation and oxidative stress.

103 eicosapentaenoic acid (EPA), which inhibits PKC beta II activity and colon carcinogenesis, causes in

104 st that TNF-alpha-induced apoptosis involves PKC-beta and then ceramide and, in turn, caspase-1 and/o

105 hat oral pharmacological therapies involving PKC beta-isoform-selective inhibitors may prove efficaci

106 o acids 501-511 of tyrosinase containing its PKC-beta phosphorylation site, a presumptive PKC-beta ps

107 hosphorylated by the serine/threonine kinase PKC-beta.

108 to nonpigmented human melanoma cells lacking PKC-beta lead to the phosphorylation and activation of t

109 By immunoelectron microscopy, PKC-beta but not PKC-alpha was closely associated with t

110 by the overexpression of a dominant-negative PKC beta 2 isoform but not by the expression of PKC alph

111 ative PKC alpha, but not a dominant-negative PKC beta or delta, abrogated PKD1-mediated AP-1 activati

112 ed in unfractionated epidermal cells, and no PKC-beta 2 signal was detected in epidermal cells deplet

113 '-dimethanol dimethyl ether [HBDDE]) but not PKC-beta II (LY379196) decreased O(2)(-) release and p47

114 The addition of PKC beta selective inhibitor (LY333531) to cultured mesa

115 el and PKC activity as well as the amount of PKC beta II isoform in ASMCs cultured with elevated gluc

116 Association of PKC beta 2 isoform with retinoblastoma protein was disco

117 overlay assays confirmed the association of PKC beta and PKC theta with spectrin following its reorg

118 The potential functional consequences of PKC beta-induced retinoblastoma phosphorylation could in

119 egative PKK was reverted by co-expression of PKC beta I, suggesting a functional association between

120 Expression of PKC beta II in the colon of transgenic mice leads to hyp

121 bits ATP dependent competitive inhibition of PKC beta I and is selective for PKC in comparison to oth

122 76- and 61-fold selective for inhibition of PKC beta I and PKC beta II in comparison to PKC alpha, r

123 to be a competitive reversible inhibitor of PKC beta 1 and beta 2, with a half-maximal inhibitory co

124 ovel, orally effective specific inhibitor of PKC beta isoform (LY333531) normalized many of the early

125 the series are also selective inhibitors of PKC beta.

126 colon cancer cells led to elevated levels of PKC beta 1 or PKC beta 2 protein and PKC beta kinase act

127 ion of ERK3 in cells with elevated levels of PKC beta 1 or PKC beta 2.

128 The expression levels of PKC beta.

129 l endothelial cells by the overexpression of PKC beta 1 or beta 2 isoforms and inhibited significantl

130 the RACK-1-binding site in the C2 region of PKC beta induced modification of Ser218-Leu-Asn-Pro-Glu-

131 al domain in the carboxyl-terminal region of PKC beta, which is involved in directing isoenzyme-speci

132 evel of PKC alpha did not change and that of PKC beta decreased in the cytosol of the ipsilateral hip

133 The stoichiometries of thionylation of PKC beta mediated by [35S]GS-DSMO and [35S]GS-DSDO were

134 LLO-dependent translocation of PKC beta I to early endosomes also occurs between 1 and

135 locker SK&F 96365 inhibited translocation of PKC beta II but not PKC delta.

136 phery of J774 cells and for translocation of PKC beta II to early endosomes beginning within the firs

137 PKC-beta(-/-) mice to examine the action of PKC-beta isoforms in diabetes-induced oxidative stress a

138 a in diabetes is partly due to activation of PKC-beta and -delta isoforms, suggesting that inhibition

139 e differentiation involves the activation of PKC-beta and expression of extracellular matrix proteins

140 n blot analysis confirmed the association of PKC-beta with melanosomes.

141 <0.04), indicating a greater contribution of PKC-beta to total PKC activity in failed hearts.

142 hat PRKX gene expression is under control of PKC-beta; hence PRKX is likely to act downstream of this

143 essed in LCs, and (ii) the downregulation of PKC-beta 2 is associated with impaired LC function with

144 ress may also mediate the adverse effects of PKC-beta isoforms by the activation of the DAG-PKC pathw

145 2 activity and demonstrate the importance of PKC-beta as a positive modulator of secretion, cPLA2 act

146 To determine whether inhibition of PKC-beta activity decreases pigmentation, paired culture

147 d was partially blocked by the inhibition of PKC-beta and PKC-delta.

148 Inhibition of PKC-beta promoted cell death in B lymphomas characterize

149 ssels, can be modulated by the inhibition of PKC-beta.

150 We identified low-nanomolar inhibitors of PKC-beta with good to excellent selectivity vs other PKC

151 C-dependent pathway and that introduction of PKC-beta into nonpigmented human melanoma cells lacking

152 Lack of PKC-beta can protect against diabetes-induced renal dysf

153 To determine whether the decreased level of PKC-beta 2 within LCs was associated with an alteration

154 application of TPA resulted in a 90% loss of PKC-beta 2 within 6 h without a decrease in the number o

155 tern blot analysis confirmed the presence of PKC-beta 2 in LCs.

156 ive autoregulation involves up-regulation of PKC-beta promoter activity by constitutive PKC signaling

157 N'-tetraacetic acid blocked translocation of PKC-beta(1) and -beta(2).

158 ein blocked glucose-induced translocation of PKC-beta(1) and -delta, whereas chelation of intracellul

159 to myocyte cultures blocked translocation of PKC-beta(1), -beta(2), -delta, and -epsilon.

160 ate blocked glucose-induced translocation of PKC-beta(2), -delta, and -zeta.

161 ent with soluble CD40L and were dependent on PKC-beta and PKC-gamma, respectively.

162 al PKC isoforms expressed in platelets, only PKC beta co-immunoprecipitated with alpha(IIb)beta(3) in

163 ells led to elevated levels of PKC beta 1 or PKC beta 2 protein and PKC beta kinase activities in the

164 cells with elevated levels of PKC beta 1 or PKC beta 2.

165 for protein kinases C beta 1 (PKC beta 1) or PKC beta 2 into differentiated colon cancer cells led to

166 tives that overexpressed either PKC alpha or PKC beta 1.

167 slocation, but not ARF1, ARF6, PKC alpha, or PKC beta translocation.

168 -HEK 293 cells transfected with PKCa lpha or PKC beta(I).

169 creased PKCepsilon, but no changes in PKA or PKC-beta levels in the SHR myocardium.

170 retinal hemodynamic abnormalities by an oral PKC beta inhibitor.

171 l ischemia in transgenic mice overexpressing PKC beta 2 isoform and a significant decrease in retinal

172 Transgenic mice overexpressing PKC-beta isoform in the myocardium developed cardiac hyp

173 ted the relation between the polyol pathway, PKC-beta, ROS, JAK2, and Ang II in the development of di

174 mma and PKC pathway, involving predominately PKC-beta isoform activation in endothelial cells.

175 PKC-beta phosphorylation site, a presumptive PKC-beta pseudosubstrate, gave similar results.

176 Our data define a procarcinogenic PKC beta II --> Cox-2 --> TGF-beta signaling axis within

177 fibrinogen caused green fluorescent protein-PKC beta I to associate with alpha(IIb)beta(3) and to co

178 with a PKC-beta expression plasmid restored PKC-beta levels and PMA inducibility of cell adhesion an

179 n of TGF-beta1-mediated transcription in RIE/PKC beta II cells.

180 tores TGF beta-mediated transcription in RIE/PKC beta II cells.

181 in Cox-2 protein and PGE2 production in RIE/PKC beta II cells.

182 LY333531, a selective PKC-beta inhibitor, significantly decreased PKC activity

183 A highly specific PKC beta inhibitor, LY379196, blocked dopamine efflux th

184 The effectiveness of a specific PKC-beta isoform inhibitor introduced directly into the

185 Furthermore, all these molecules (spectrin, PKC beta, PKC theta, and receptor for activated C kinase

186 kinase C-beta (PKC-beta) and several stable PKC-beta transfectants, we found that PRKX gene expressi

187 he initial calcium signal and the subsequent PKC beta II translocation.

188 t evidence that DAG elevation and subsequent PKC-beta isoform activation are the primary biochemical

189 id and D-alpha-tocopherol and, surprisingly, PKC beta-isoform inhibition.

190 ogether, our results indicate that targeting PKC-beta has the potential to disrupt signaling from the

191 Our data demonstrate that PKC beta II promotes colon cancer, at least in part, thr

192 In our studies we observed that PKC beta was predominantly expressed in the neocortex, i

193 Here we report that PKC beta II induces the expression of cyclooxygenase typ

194 We conclude that PKC-beta activates tyrosinase directly by phosphorylatin

195 Here, we demonstrate that PKC-beta is specifically required for B cell receptor (B

196 lure, further supporting the hypothesis that PKC-beta isoform activation can cause vascular dysfuncti

197 escent labeling of phagosomes indicated that PKC-beta and PKC-zeta were the isoforms that are not pho

198 ermal cells depleted of LCs, indicating that PKC-beta 2 is expressed exclusively in LCs within the ep

199 could no longer be detected, suggesting that PKC-beta 2 is more sensitive to downregulation, and/or s

200 The PKC beta knock-out animals exhibited a loss of learning,

201 ts reveal cooperative Ca(2+) binding for the PKC beta C2 domain but not for the PKC alpha or PKC gamm

202 ning, we characterized mice deficient in the PKC beta gene using anatomical, biochemical, physiologic

203 sion pattern and behavioral phenotype in the PKC beta knock-out animals indicate a critical role for

204 lohexadecene++ +-1,3(2H)-dione, inhibits the PKC beta I (IC50 = 4.7 nM) and PKC beta II (IC50 = 5.9 n

205 The PKC-beta isoform played a critical role in the expressio

206 role in the expression of MMPs, because the PKC-beta inhibitor hispidin reduced ox-LDL-induced activ

207 cells with exogenous ceramides bypassed the PKC-beta deficiency and induced apoptosis, which was als

208 interactions, whereas docking of either the PKC-beta or the Syt-IA domain to anionic lipids is trigg

209 d 10-fold higher Ca2+ concentrations for the PKC-beta and Syt-IA C2 domains ([Ca2+](1/2) = 4.7, 16, 4

210 PLA2-alpha domain, compared to 13 ms for the PKC-beta domain and only 6 ms for the Syt-IA domain.

211 Intravitreal injection of the PKC-beta inhibitor (LY333531) at 10(-5) M in diabetic ra

212 In this process, activation of the PKC-beta subunit plays an important signaling role.

213 tudy, we have extended the analysis of these PKC beta transfectants to the mitogen-activated protein

214 Conversely, antisera to PKC beta(I) and PKC beta(II) but not PKC alpha or PKCg a

215 rt and suggests that this increase is due to PKC beta-mediated translocation of cytosolic GLUT1 to th

216 Both antisense oligos to PKC-beta and -alpha as well as small interfering RNA (si

217 siRNA to PKC-beta and -alpha also significantly decreased NF-kapp

218 Thus, while overexpression of transfected PKC beta does not lead to overexpression of ERK3, it doe

219 elial (RIE) cells in vitro and in transgenic PKC beta II mice in vivo.

220 at 63 kDa, the size of ERK3, in each of two PKC beta 1 and each of two PKC beta 2 transfectants comp

221 3, in each of two PKC beta 1 and each of two PKC beta 2 transfectants compared with the vector contro

222 We used PKC-beta(-/-) mice to examine the action of PKC-beta iso

223 ation of PKC alpha into the nucleus, whereas PKC beta 1 remained in the cytoplasm.

224 ies are now in progress to determine whether PKC-beta inhibition can prevent diabetic complications.

225 n the basis of its specific interaction with PKC beta.

226 anced in hDAT-HEK 293 cells transfected with PKC beta(II) as compared with hDAT-HEK 293 cells alone,

227 Moreover, treatment with PKC beta inhibition is effective to normalize diabetes o

228 However, with PKC-beta and PKC-gamma the only detectable translocation

229 However, transfection with PKC-beta antisense oligonucleotide, preincubation with a

230 Treatment with PKC-beta isoform-specific inhibitor (LY333531) or insuli