ライフサイエンスコーパス: pseudosubstrate

1 d-type aPKC, but not a construct lacking the pseudosubstrate.

2 Ch and PMA was blocked by Ro-31-8425 or beta-pseudosubstrate.

3 on and dephosphorylation requires an exposed pseudosubstrate.

4 dies suggest that PIP3 binds directly to the pseudosubstrate.

5 n cAMP-dependent protein kinase upon binding pseudosubstrate.

6 not by the alpha, delta, or alpha beta gamma pseudosubstrate.

7 ylation, as it was inhibited by the PKC-zeta pseudosubstrate.

8 rate but not by the alpha, delta, or epsilon pseudosubstrate.

9 hows desulfation activity toward arylsulfate pseudosubstrates.

10 Fs) by treating C2C12 myotubes with PKCtheta pseudosubstrates.

11 A PKCzeta pseudosubstrate, a specific blocker of aPKC activity, an

12 activity by myristoylated PKC (zeta/lambda) pseudosubstrate, a specific inhibitor of PKCzeta, and Go

13 This pseudosubstrate affinity assay can detect variations in

14 peptide, myristoylated protein kinase C-zeta pseudosubstrate, also significantly decreased the entero

15 interaction activates aPKC by displacing the pseudosubstrate, although full activity requires the Par

16 The pseudosubstrate and C1a domains, however, are minimally

17 Myristoylated PKC (zeta/lambda) pseudosubstrate and DN PKCzeta also inhibited cAMP-induc

18 atalysis; and exposure of the amino-terminal pseudosubstrate and masking of the carboxyl terminus acc

19 We find that Acm1 uses pseudosubstrate and other sequence motifs to bind and in

20 Moreover, although substrates/pseudosubstrate and products independently close the act

21 nzyme activity in vitro by both the PKC-zeta pseudosubstrate and RO 31-8220 correlated well with inhi

22 gulatory region of PKCepsilon containing the pseudosubstrate and zinc finger-like sequences was found

23 ptical methods that often require the use of pseudosubstrates and associated dyes.

24 tanol, cell-permeable myristoylated PKC-zeta pseudosubstrate, and expression of kinase-inactive RAF,

25 This differs from the more usual pseudosubstrate approach to enzyme inhibition.

26 dicating that AutoN does not act as a simple pseudosubstrate as suggested previously.

27 In living cells, zVAD-FMK, a pseudosubstrate aspartase inhibitor, blocked the activit

28 The effects of substrate/pseudosubstrate (ATP and PKI(5-24)), a fragment of prote

29 dependent/conformational-dependent relief of pseudosubstrate autoinhibition.

30 y a short junction sequence which contains a pseudosubstrate autoinhibitor.

31 th kinase was mapped to what appears to be a pseudosubstrate autoinhibitory domain at the extreme car

32 lly falls into two categories: regulation by pseudosubstrate autoinhibitory domains, and remodeling o

33 Some compounds such as pseudosubstrate-based peptide inhibitor binds to the pep

34 GIYWHHY, we designed and synthesized several pseudosubstrate-based peptide inhibitors.

35 in, that demonstrate the molecular basis for pseudosubstrate binding to the active state with phospho

36 impairs eIF2alpha phosphorylation and viral pseudosubstrate binding.

37 Both RO 31-8220 and myristoylated PKC-zeta pseudosubstrate blocked insulin-induced activation and a

38 mtide-2-related inhibitory peptide (AIPm), a pseudosubstrate blocker of CaMKII, whereas axotomized ne

39 tion of ESO cells was reduced by the epsilon pseudosubstrate but not by the alpha, delta, or alpha be

40 ES cells was reduced by the alpha beta gamma pseudosubstrate but not by the alpha, delta, or epsilon

41 /methionine is cleaved at the amino-terminal pseudosubstrate by the endoproteinase Arg-C.

42 he complex formation of C1s with its natural pseudosubstrate, C1 inhibitor (C1 inh), and promotion of

43 (C1a, C1b, and C2) appears to strengthen the pseudosubstrate-catalytic domain interaction in a nucleo

44 ing to PKCgamma was initially prevented by a pseudosubstrate clamp, which kept the diacylglycerol-bin

45 ion or exposure for 1 hour to myristoylated, pseudosubstrate-derived peptide inhibitors against PKCal

46 Pseudosubstrate-derived peptides, like ZIP, are thought

47 ticity and memory have relied on the PKCzeta pseudosubstrate-derived zeta-inhibitory peptide (ZIP).

48 h RVPO (>12 fold), and phosphorylated in the pseudosubstrate domain at the Ser-411, Thr-421, and Ser-

49 g of the active PKA catalytic subunit to its pseudosubstrate domain inhibitor (PKI) fused with glutat

50 We find that whereas the pseudosubstrate domain is necessary for autoinhibition i

51 hobic residue (Val(125)) within the putative pseudosubstrate domain of cGKII.

52 e corresponding to the unique PKCiota/lambda pseudosubstrate domain was introduced into an in vitro a

53 cted residues in the putative autoinhibitory pseudosubstrate domain, as well as threonine 389.

54 egulatory elements, including the inhibitory pseudosubstrate domain, consequently rendering the kinas

55 horylation sites at Thr(141) adjacent to the pseudosubstrate domain, Thr(218) in the C1A-C1B interdom

56 ain bears a striking resemblance to the SOCS pseudosubstrate domain, we examined whether Jak-2 associ

57 58 was examined due to its proximity to the pseudosubstrate domain.

58 While the action of pseudosubstrate domains can be explained by simple compe

59 alytic, kinase extension, and autoinhibitory pseudosubstrate domains, was identified.

60 Ca2+-binding, diacylglycerol-activation and pseudosubstrate domains.

61 (EPSP) synthase has been examined using the pseudosubstrates, (E)- and (Z)-3-fluorophosphoenolpyruva

62 HF), the product tetrahydrofolate (THF), the pseudosubstrate folate, reduced and oxidized NADPH cofac

63 toylated peptide based on the autoinhibitory pseudosubstrate fragment of the atypical PKCzeta, zeta i

64 KI), an inhibitor of a novel PKC (an nPKCeta pseudosubstrate fragment), and an antioxidant (melatonin

65 ides the energy to release an autoinhibitory pseudosubstrate from the active site.

66 may reflect the energy required to expel the pseudosubstrate from the substrate binding cavity.

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

68 or substrates of AMPK, inhibit the kinase as pseudosubstrates in a Rapamycin-regulated fashion in vit

69 S-Adenosylhomocysteine acted as a pseudosubstrate, in that it did not undergo either acyla

70 Inhibition of PKC-zeta using PKC-zeta pseudosubstrate inhibited IL-1beta-stimulated increases

71 Inhibition of PKC-theta and PKC-zeta using pseudosubstrates inhibited IL-1beta-stimulated activatio

72 PC/C inhibitors have been reported to act as pseudosubstrates, inhibiting the APC/C by preventing sub

73 This pseudosubstrate inhibition of AMPK by LiRP proteins redu

74 ty of ubiquitinatable lysines contributes to pseudosubstrate inhibition of APC(Cdh1).

75 the PKR kinase domain can drastically impact pseudosubstrate inhibition while leaving substrate phosp

76 Pseudosubstrate inhibition, a commonly observed mechanis

77 p78 inhibits PKA and PRKX kinase activity by pseudosubstrate inhibition.

78 Using a selective, cell-permeable zeta-pseudosubstrate inhibitor at concentrations that block p

79 erminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide bindi

80 ential and that soluble BubR1 functions as a pseudosubstrate inhibitor of APC/C(Cdc20) during interph

81 These findings implicate Mad3p as a pseudosubstrate inhibitor of APCCdc20, competing with AP

82 We detected homology between a cellular pseudosubstrate inhibitor of PKA, the protein kinase inh

83 because it was not inhibited by the specific pseudosubstrate inhibitor of PKC, PKC(19-31), and it was

84 ing NMDA receptors using an isoform-specific pseudosubstrate inhibitor of PKCzeta.

85 nalysis on the vaccinia virus K3L protein, a pseudosubstrate inhibitor of PKR.

86 Addition of a pseudosubstrate inhibitor of the Ca2+-calmodulin-depende

87 r, in the presence of an N-myristoylated PKC pseudosubstrate inhibitor peptide (MyrPsiPKC-I(19-27)),

88 vation of Kv3.3 currents, and a specific PKC pseudosubstrate inhibitor peptide prevented the effects

89 phosphatidylserine and blocked by excess PKC pseudosubstrate inhibitor peptide.

90 In permeabilized 3T3-L1 cells, addition of pseudosubstrate inhibitor peptides of casein kinase II (

91 he atypical PKCzeta by myristoylated PKCzeta pseudosubstrate inhibitor significantly decreased the A(

92 PhK13 has been proposed to function as a pseudosubstrate inhibitor with Cys-308 occupying the sit

93 ither bisindolylmaleimide-I or a peptide PKC pseudosubstrate inhibitor, and COX-2 mRNA and protein we

94 y been shown to inhibit Cdc20 by acting as a pseudosubstrate inhibitor, but in this paper, we show th

95 Inhibition of PKCzeta by its pseudosubstrate inhibitor, or its siRNA, or dominant neg

96 p-regulation, an effect inhibited by the PKC pseudosubstrate inhibitor, PKC19-36.

97 Furthermore, excess amounts of the pseudosubstrate inhibitor, PKI(5-24), had no effect on t

98 effects were abolished by a PKCzeta-specific pseudosubstrate inhibitor.

99 -alkylating agents (e.g., temozolomide) with pseudosubstrate inhibitors (such as O(6)-benzylguanine)

100 h untreated and ionophore-treated cells, but pseudosubstrate inhibitors only bound to TF-factor VIIa

101 Pharmacological tools and pseudosubstrate inhibitors suggested that these kinases

102 tantial differences in the concentrations of pseudosubstrate inhibitors which rescued cells from SOD1

103 model for how E3 substrates evolve to become pseudosubstrate inhibitors.

104 activity, as intrathecal delivery of a zeta-pseudosubstrate inhibitory peptide (PKCzeta-PS) 35 min f

105 and PIP3 current activation is blocked by a pseudosubstrate inhibitory peptide of atypical PKC but n

106 Intrahemocoel injections of the pseudosubstrate inhibitory peptide ZIP (zeta inhibitory

107 vation by PMA and inhibition of PKC with the pseudosubstrate inhibitory peptide.

108 and for residues 102-115, which include the pseudosubstrate inhibitory site, support the prediction

109 the idea that residues conserved between the pseudosubstrate K3L protein and the authentic substrate

110 nsulin, but not PIP(3), activated truncated, pseudosubstrate-lacking forms of PKC-zeta and PKC-lambda

111 Moreover, treatment with PKClambda/zeta pseudosubstrate lead to significant reduction of FGF2-me

112 However, truncation of a pseudosubstrate-like sequence in the C-terminus of DCK1

113 tate) and the inhibitors (high magnesium and pseudosubstrate) locking it into discrete minima (dynami

114 1+ by ran1+ and suggest that mei3+ employs a pseudosubstrate mechanism for its inhibitory function.

115 ructure of the Grp1 Sec7-PH tandem reveals a pseudosubstrate mechanism of autoinhibition in which the

116 E2, and these results are consistent with a pseudosubstrate mechanism of inhibition of eIF2alpha kin

117 emonstrate that instead of acting through a "pseudosubstrate" mechanism as previously hypothesized, E

118 e (-59AQKQAS-) that is amino-terminal to the pseudosubstrate motif (-74KRQAI-).

119 re regulated by an N-terminal autoinhibitory pseudosubstrate motif centered on a critical proline res

120 within its NH(2)-terminal regulatory half, a pseudosubstrate motif that occupies the kinase active si

121 First, it blocks PKAC activity via a pseudosubstrate motif, akin to the mechanism employed by

122 bitor Acm1, which incorporates D and KEN box pseudosubstrate motifs, we describe the molecular basis

123 ave previously shown that the autoinhibitory pseudosubstrate must be removed from the active site in

124 and (d) react with the low molecular weight pseudosubstrate, O6-benzylguanine.

125 ic surface, resulting in displacement of the pseudosubstrate of aPKC and re-engagement in the substra

126 These data support a model in which the pseudosubstrate of aPKCs is tethered to the acidic surfa

127 TR internalization by more than 50%, whereas pseudosubstrates of cyclic AMP-dependent kinase A, prote

128 emplate that acts as a reversible inhibitor (pseudosubstrate) of redox proteins.

129 rotein kinase C-zeta (PKC-zeta) inhibitor (a pseudosubstrate oligopeptide), but not a PKC-alphabeta i

130 protein kinase C zeta (PKC zeta) inhibitors (pseudosubstrate or small interfering RNA silencing).

131 hat purified recombinant PelA hydrolyzed the pseudosubstrate p-nitrophenyl acetate in vitro, and site

132 We first used the pseudosubstrate peptide (0.1 micromol/L in the pipette),

133 Strikingly, the enzyme is inhibited by the pseudosubstrate peptide Ala-Cys(-S-GlcNAc)-Ala, and has

134 Both the pseudosubstrate peptide and kinase-dead PKCiota/lambda i

135 Use of PKC agonists and isozyme-specific pseudosubstrate peptide antagonists suggested a role for

136 nanopore sensor for Pim kinases that bears a pseudosubstrate peptide attached by an enhanced engineer

137 rat kidney cells incubated with Rab2 and the pseudosubstrate peptide displayed abundant swollen or di

138 Addition of PKC-zeta pseudosubstrate peptide in vitro or myristoylated peptid

139 as prevented by intracellular perfusion of a pseudosubstrate peptide inhibitor for aPKCs.

140 This depression was partially blocked by a pseudosubstrate peptide inhibitor of cGMP-dependent prot

141 ation by DAG was specifically inhibited by a pseudosubstrate peptide inhibitor of cPKCs (PKC alpha(22

142 inase activates the subunit for binding to a pseudosubstrate peptide inhibitor of protein kinase A.

143 A pseudosubstrate peptide inhibitor of the atypical PKCs (

144 However, a pseudosubstrate peptide inhibitor specific for PKC-zeta

145 A cell-permeable PKCzeta pseudosubstrate peptide inhibitor was capable of blockin

146 substrate phosphorylation, with and without pseudosubstrate peptide inhibitor.

147 cells treated with a cell-permeable PKCzeta pseudosubstrate peptide inhibitor.

148 ion of protein kinase C activity utilizing a pseudosubstrate peptide sequence blocked IRES activity d

149 CTD can be inhibited specifically by a CDK7 pseudosubstrate peptide that also inhibits transcription

150 ihydroouabain to inhibit alpha2/3 and a zeta-pseudosubstrate peptide to inhibit PKMzeta.

151 When PKC zeta-specific inhibitory pseudosubstrate peptide was introduced into LLC-MK2 cell

152 Marinobufagenin, dihydroouabain, and zeta-pseudosubstrate peptide were used to determine if PKMzet

153 n 4% of the phosphorylation of the PKC-alpha pseudosubstrate peptide).

154 specific inhibitor (a myristoylated PKCzeta pseudosubstrate peptide).

155 inase, Rp-8Br-PET-cGMPS, KT5823, and a novel pseudosubstrate peptide, all block LTD.

156 orylation, or by intracellular delivery of a pseudosubstrate peptide, also disrupts sarcomeric organi

157 d 8, stimulated phosphorylation of the alpha-pseudosubstrate peptide, and in primary mouse keratinocy

158 cells in the presence of a protein kinase C pseudosubstrate peptide, but not a control peptide, inhi

159 ferent PDK1 inhibitors-BX-912 and a specific pseudosubstrate peptide-destabilized PKCiota.

160 tion similar to that seen for C with a bound pseudosubstrate peptide.

161 /-7.4% but was not affected by the scrambled pseudosubstrate peptide.

162 activators of PKC and not affected by a PKC pseudosubstrate peptide.

163 Pharmacologic agents, isoform-selective pseudosubstrate peptides, and antisense oligonucleotides

164 ine phospholipase C (PC-PLC), PKC (including pseudosubstrate peptides, chelerythrine, and the alpha/b

165 KC-alpha activation by classical inhibitors, pseudosubstrate peptides, or the overexpression of domin

166 ease), a CaM-binding peptide, or CaM-KII/PKC pseudosubstrate peptides.

167 P and was therefore used to assess whether a pseudosubstrate perturbed the rate of holoenzyme dissoci

168 he region within PKR that interacts with the pseudosubstrate, pK3, is the same region that interacts

169 tion by a Src kinase inhibitor and a PKCzeta-pseudosubstrate prevented eritoran-induced apoptosis.

170 The use of a PKCzeta pseudosubstrate prevented IL-1 from increasing ROS great

171 KA inhibitor (PKI) containing a specific PKA pseudosubstrate, R-R-N-A, was subcloned into a pTREX vec

172 Incubation with an aPKC pseudosubstrate recapitulates the phenotype of PKCiota k

173 f RSK1 competed with PKAc for binding to the pseudosubstrate region (amino acids 93-99) of PKARIalpha

174 ased on the endogenous zeta protein kinase C pseudosubstrate region block agonist-induced adhesion to

175 e PKAc, which requires Arg-95 and -96 in the pseudosubstrate region of PKARIalpha for their interacti

176 Thus, by competing for binding to the pseudosubstrate region of PKARIalpha, RSK1 regulates PKA

177 hat contains a sequence corresponding to the pseudosubstrate region of PKC-alpha (P1) partially rever

178 says, but PKC alpha constructs that lack the pseudosubstrate region or constructs of the whole cataly

179 We also find that PAK6 is regulated by the pseudosubstrate region, indicating a common type II PAK

180 as measured by phosphorylating the PKC-delta pseudosubstrate region-derived substrate was also reduce

181 -zeta (aPKCzeta), which lacks the N-terminal pseudosubstrate regulatory domain.

182 itutively autoinhibited, but mutation of the pseudosubstrate releases this inhibition and causes incr

183 I to the cell-free reactions containing CKII pseudosubstrates reversed the endocytosis block, suggest

184 l change, which displaces the amino-terminal pseudosubstrate segment from the active site.

185 terminal regulatory domain, which includes a pseudosubstrate segment that plugs the active site.

186 Our studies identify the core pseudosubstrate sequence (residues 297-300) but reveal t

187 ubstrate suggests that basic residues in the pseudosubstrate sequence are required for maintaining aP

188 We propose that in the absence of AMP this pseudosubstrate sequence binds to the active site groove

189 ially associated with the C subunit with the pseudosubstrate sequence docked in the active site cleft

190 ormational change in which an autoinhibitory pseudosubstrate sequence is released from the active sit

191 kinase C adopts a conformation in which its pseudosubstrate sequence is removed from the active site

192 kinase C adopts a conformation in which its pseudosubstrate sequence is removed from the active site

193 l five (or certain) arginine residues in the pseudosubstrate sequence of PKC-iota by site-directed mu

194 a myristoylated peptide corresponding to the pseudosubstrate sequence of protein kinase inhibitor (my

195 active site is blocked by binding either the pseudosubstrate sequence or a heterologous substrate.

196 ling that precursor protein kinase C has its pseudosubstrate sequence removed constitutively.

197 d in the central region of Acm1 constitute a pseudosubstrate sequence required for APC(Cdh1) inhibiti

198 hibitory peptide (ZIP) based on the PKC-zeta pseudosubstrate sequence reverses established LTP in vit

199 itive inhibition of substrate binding with a pseudosubstrate sequence within the holoenzyme.

200 diminished by autophosphorylation near this pseudosubstrate sequence.

201 M to residues associated with the inhibitory pseudosubstrate sequence.

202 hus, it is likely that Mei3-RKDIII defines a pseudosubstrate sequence.

203 hosphorylatable substrate-like sequence or a pseudosubstrate sequence.

204 N-Myristoylated peptides derived from the pseudosubstrate sequences of PKC isozymes were used to i

205 plays a high degree of conservation with the pseudosubstrate sequences of the protein kinase C (PKC)

206 and -eta were very similar to the endogenous pseudosubstrate sequences of these PKC isozymes, indicat

207 le of basic arginine residues common to aPKC pseudosubstrate sequences.

208 ugh PhK13-1 does not appear to function as a pseudosubstrate, several specificity determinants employ

209 The italicized amino acids form a putative pseudosubstrate site (Ser is replaced with Ala), which t

210 es that are juxtaposed to the autoinhibitory pseudosubstrate site in cGMP-dependent protein kinase ty

211 te that a conserved serine juxtaposed to the pseudosubstrate site in type I PKGs contributes importan

212 the pseudosubstrate site, but Arg-75 in the pseudosubstrate site is critical for autoinhibition.

213 h active kinases, kinase-dead PKC eta with a pseudosubstrate site mutation designed to give an active

214 res all four Arg residues (Arg-93-96) in the pseudosubstrate site of PKARIalpha.

215 from SLE T cells, one located adjacent to a pseudosubstrate site of the RI alpha subunit and the oth

216 wo copies of the cAMP-dependent kinase (PKA) pseudosubstrate site RRGAI.

217 lation site of Ibeta cGK is well outside the pseudosubstrate site, but Arg-75 in the pseudosubstrate

218 cGK enhances proteolysis within and near the pseudosubstrate site; treatment of dimeric cGK with thre

219 The domain containing PKA pseudosubstrate sites at the N terminus of PDE7A1 mediat

220 s as a conformational switch to position the pseudosubstrate so that it blocks the active site, a con

221 Pseudosubstrate-specific peptides with attached myristic

222 nitiated by the addition of Mg(2+) ions or a pseudosubstrate strand to the ribozyme, and the ensuing

223 ract the inhibitory effects of the exogenous pseudosubstrate suggests that basic residues in the pseu

224 e (FMP) on SERCA, producing a phosphorylated pseudosubstrate tethered to the nucleotide-binding site

225 Ebp2 thus acts like a pseudosubstrate that directly recruits Fbw7 to nucleoli.

226 ddition of the exogenous arginine-containing pseudosubstrate tridecapeptide to inhibit this constitut

227 However, pseudosubstrates used to inhibit AGT activity have had l

228 paradoxical effects of the PKR mutations on pseudosubstrate vs. substrate interactions reflect diffe

229 sponsiveness to PIP3 was seen when exogenous pseudosubstrate was used to inhibit mouse liver PKC-lamb

230 ibits eIF-2alpha kinases by functioning as a pseudosubstrate, we observed that K3L directly interacte

231 is reversibly regulated by an autoinhibitory pseudosubstrate, which blocks the active site of the enz

232 A was also observed in the reaction with the pseudosubstrate, (Z)-3-fluorophosphoenolpyruvate, strong