ライフサイエンスコーパス: PP5

1 clophilin CyP-40 and the protein phosphatase PP5).

2 TPR domain of phosphoprotein phosphatase 5 (PP5).

3 -PP5 complexes and membrane translocation of PP5.

4 th failed to cause membrane translocation of PP5.

5 nd the Ser/Thr-directed protein phosphatase, PP5.

6 ls on ASK1 dephosphorylation was mediated by PP5.

7 es, as potential physiological regulators of PP5.

8 aired functional interaction between ATR and PP5.

9 , thought to be a physiological substrate of PP5.

10 of GR-associated FKBP51 and replacement with PP5.

11 sites; and Ser(262) was the poorest site for PP5.

12 ociated with reduced phosphatase activity of PP5.

13 horylation were dependent upon expression of PP5.

14 immunophilin CyP40, and protein phosphatase PP5.

15 FKBP52 or CyP40, or the protein phosphatase PP5.

16 s reduced by 80% for rA2-PP2 and 95% for rA2-PP5.

17 tic peptide bound to the catalytic domain of PP5.

18 ed two potential physiological activators of PP5.

19 ted in maintaining the low basal activity of PP5.

20 ase, as well as a serine protease inhibitor, PP5.

21 ximal response obtainable in the presence of PP5.

22 of the TPR domain of a protein phosphatase, PP5.

23 pletely reversed following reintroduction of PP5.

24 e known roles and identified new actions for PP5.

25 pared the properties of BUBR1(1-204) and TPR-PP5(16-181) at air/water interfaces and found that both

26 Here, we show that protein phosphatase 5 (PP5), a nuclear receptor co-chaperone, reciprocally modu

27 , we demonstrate that protein phosphatase 5 (PP5), a previously documented component of the Hsp90 cha

28 , to help evaluate the biological actions of PP5, a Cre/loxP-conditional mouse line was generated.

29 Gene knockdown of PP5 abolished the estrogen-mediated suppression of GR ph

30 inting to Ser-112 as an important residue of PP5 action.

31 We also examined the effect of lipoxin A4 on PP5 activation by IL-2 plus IL-4.

32 cts of chain length and of the CoA moiety on PP5 activation.

33 during HRI maturation/activation, while the PP5 activators arachidonic and linoleic acid repressed H

34 ses apoptosis through positive regulation of PP5 activity and suppression of cellular stress.

35 Down-regulation of PP5 activity by rapamycin coordinately activated ASK1, l

36 Interestingly, reduced PP5 activity exerts differential effects on the formatio

37 n AD might result in part from the decreased PP5 activity in the diseased brains.

38 fficacy of Hsp90 inhibitors by regulation of PP5 activity in tumors.

39 erizing the effects of compounds that impact PP5 activity in vitro.

40 ted the dependence of GCR phosphorylation on PP5 activity, and 3) revealed that PP5 is a target of th

41 ycin inhibits mTOR signaling, also inhibited PP5 activity, caused rapid dissociation of PR72, and act

42 To identify residues involved in regulating PP5 activity, we performed scanning mutagenesis of its N

43 domain (C90), we investigated its effect on PP5 activity.

44 udies with siRNA targeting PP5 indicate that PP5 acts to suppress the phosphorylation of MKK4 (Thr-26

45 nse when PP5 expression is inhibited, or (2) PP5 acts where p53-mediated and GR-induced signaling net

46 Serine/threonine protein phosphatase-5 (PP5) affects many signaling networks that regulate cell

47 aled that the constitutive overexpression of PP5 affords E(2)-dependent MCF-7 cells with the ability

48 p90 (MEEVD motif) binds to the TPR domain of PP5 almost 3-fold higher affinity than Hsp70 (IEEVD moti

49 Here we show that the expression of PP5, an evolutionarily conserved Ser/Thr phosphatase tha

50 ase in polyamine levels via de-inhibition of PP5 and accelerated dephosphorylation and deactivation o

51 hese results demonstrate that Hsp70 recruits PP5 and activates its phosphatase activity which suggest

52 /Cip1) via a mechanism that is suppressed by PP5 and associated with the phosphorylation of p53 at Se

53 However, PP5 and ERK activity regulates the phosphorylation state

54 to L929 cells, the GR in COS interacted with PP5 and FKBP51, while PR interacted with FKBP52.

55 und in the cytoplasm in a complex containing PP5 and FKBP51, while the GR of WCL2 cells was nuclear a

56 e GR of WCL2 cells was nuclear and contained PP5 and FKBP52.

57 netics of dephosphoryation of phospho-tau by PP5 and found that PP5 had a K(m) of 8-13 microm toward

58 munofluorescence analysis to examine whether PP5 and glucocorticoid receptors are co-expressed at the

59 Co-localization of PP5 and glucocorticoid receptors in brain regions involv

60 glucocorticoid receptor expressing neurons, PP5 and glucocorticoid receptors were co-localized at th

61 nstrates cross-talk between estrogen-induced PP5 and GR action.

62 ith ERK2, in a manner that is independent of PP5 and MAPK/ERK kinase (MEK) activity, yet paradoxicall

63 esters might be physiological activators of PP5 and point to a potential link between fatty acid met

64 u could be a physiological substrate of both PP5 and PP2A.

65 ys a significant role only in smaller cyclic PP5 and PP6.

66 eins have been identified that interact with PP5 and regulate its activity, a possibility of its regu

67 tau is probably a physiological substrate of PP5 and that the abnormal hyperphosphorylation of tau in

68 ybrid screen revealed an interaction between PP5 and the A subunit of PP2A.

69 the protein serine-threonine phosphatase 5 (PP5) and ATM.

70 sing purified proteins, we show that FKBP52, PP5, and the PPIase domain fragment bind directly to the

71 protein 1 [AKAP149], protein phosphatase 5 [PP5], and inhibitor 2).

72 eurons and glial cells throughout the brain, PP5 appears to be primarily expressed in neurons.

73 The TPR proteins FKBP52, FKBP51, Cyp40, and PP5 are found in steroid receptor (SR) complexes, but th

74 functional implications of binding Hsp70 to PP5 are not yet clear.

75 at three basic residues in the TPR domain of PP5 are required for binding to the acidic C-terminal do

76 Lastly, mice deficient in PP5 are resistant to the negative effects of rosiglitazo

77 ill, the physiological/pathological roles of PP5 are unclear.

78 Thus, CCRK and PP5 are yin-yang regulators of T157 phosphorylation.

79 This work identifies PP5 as a fulcrum point in nuclear receptor control of th

80 mplicated the Ser/Thr protein phosphatase 5 (PP5) as an effector of Rac1 GTPase signaling, but direct

81 contain an immunophilin (FKBP52, CyP-40, or PP5) as well as dynein.

82 or the protein serine/threonine phosphatase, PP5, as an effector of Rac GTPase signaling.

83 e PP2A-B" regulatory subunit (PR72) from the PP5-ASK1 complex, which was associated with reduced phos

84 n regulating the feedback phosphorylation of PP5-associated Raf1.

85 Long-chain fatty acyl-CoA esters activated PP5 at physiological concentrations, with the saturated

86 Reduced expression of PP5 attenuated DNA-damage-induced activation of ATM.

87 the interface of the TPR domain involved in PP5 autoinhibition appears to be different from that inv

88 tion appears asymmetric with Hsp90, with one PP5 binding the dimer.

89 nd that a conserved Lys residue required for PP5 binding to hsp90 was critical for the binding of FKB

90 PP5 binds to the C-terminal domain of ASK-1, and studies

91 The TPR domain of PP5 bound specifically to a 12-kDa C-terminal fragment o

92 plexes partially depends on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity.

93 Asp-653 did not affect binding of FKBP52 or PP5 but inhibited both Hop binding and hsp90 chaperone a

94 and Asp-724 inhibited binding of FKBP52 and PP5 but not of Hop.

95 ewise, numerous neuronal populations contain PP5, but not glucocorticoid receptors.

96 Overexpression of PP5, but not the PP2A catalytic subunit, blocked rapamyc

97 To test whether activation of PP5 by polyunsaturated but not saturated fatty acids was

98 ed Rac1 provides a direct mechanism by which PP5 can be stimulated and recruited to participate in Ra

99 Thus, our results suggest that PP5 can exist in a PP2A-like heterotrimeric form contain

100 Purified PP5 can, however, be activated by partial proteolysis or

101 Serine/threonine phosphatase 5 (PP5) can act as a suppresser of p53-dependent growth sup

102 Here we report the crystal structure of the PP5 catalytic domain (PP5c) at a resolution of 1.6 A.

103 c substitution of Ser 338, or by ablation of PP5 catalytic function.

104 Collectively, these findings indicate that PP5, CKIepsilon, and cryptochrome dynamically regulate t

105 PP5 colocalizes with both cytoplasmic dynein and microtu

106 lso disrupted co-immunoprecipitation of Rac1-PP5 complexes and membrane translocation of PP5.

107 Only the NH2-terminal domain of PP5, containing all four tetratricopeptide repeats, is r

108 In addition, immunoprecipitated PP5 contains associated B subunits.

109 nother family member, protein phosphatase 5 (PP5), contains a tetratricopeptide repeat domain at its

110 rthermore, increased phosphatase activity of PP5 correlated with impaired phosphorylation of the GCR.

111 Wild-type and PP5-deficient (KO) mouse embryonic fibroblast cells were

112 roles for PP5 in fibroblasts generated from PP5-deficient embryos (PP5(-/-) mouse embryonic fibrobla

113 40 and ACTB-Cre) produced viable and fertile PP5-deficient mice.

114 PP5-dependent impairment of GRalpha function represents

115 PP5 dephosphorylated tau at all 12 Alzheimer's disease (

116 ressed by okadaic acid and by siRNA-mediated PP5 depletion, indicating that the effect of polyamine l

117 Aprataxin, an enzyme that repairs A5'pp5'DNA ends formed during abortive ligation by classic

118 ataxin, an enzyme implicated in repair of A5'pp5'DNA ends formed during abortive ligation by classic

119 The finding that PP5 downregulates an Hsp90-dependent process supports mo

120 revealed a previously unrecognized role for PP5 downstream of ATR activation in a UV light-induced r

121 ion of either p53 (e.g. with ISIS 110332) or PP5 (e.g. with ISIS 15534) in genetically identical cell

122 The PP5-ER recognition element associates with human ERs and

123 nic Ras variants and also support a role for PP5.ERK complexes in regulating the feedback phosphoryla

124 veal a novel, differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic R

125 oncogenic HRas (HRas(V12)) has no effect on PP5-ERK1 binding but selectively decreases the interacti

126 mutant proteins reveal that the formation of PP5.ERK1 and PP5.ERK2 complexes partially depends on HSP

127 utively active Rac1 promotes the assembly of PP5.ERK1/2 complexes, acute activation of ERK1/2 fails t

128 d type HRas or KRas proteins fails to reduce PP5-ERK2 binding, indicating that the effect is specific

129 (L61), but not KRas(V12), also decreases the PP5-ERK2 interaction.

130 differential responsiveness of PP5-ERK1 and PP5-ERK2 interactions to select oncogenic Ras variants a

131 ns reveal that the formation of PP5.ERK1 and PP5.ERK2 complexes partially depends on HSP90 binding to

132 Protein phosphatase 5 (PP5) exhibits low basal activity due to the autoinhibito

133 The suppression of PP5 expression (1) markedly increases the association of

134 The specific inhibition of PP5 expression ablates E(2)-mediated proliferation in MC

135 er, these studies indicate that E(2)-induced PP5 expression functions to enhance E(2)-initiated signa

136 Northern analysis revealed that E(2)-induced PP5 expression is blocked by treatment with tamoxifen, a

137 gation of an antiproliferative response when PP5 expression is inhibited, or (2) PP5 acts where p53-m

138 s leading to cell division and that aberrant PP5 expression may contribute to the development of MCF-

139 Thus, aberrant PP5 expression may have an additive effect on the develo

140 In vivo PP5 expression was also increased in the ASM bundles in

141 ration following wounding was decreased when PP5 expression was decreased using shRNA, but migration

142 Suppression of PP5 expression with ISIS 15534 also results in the hyper

143 Importantly, suppression of PP5 expression with small interfering RNA restored prope

144 hich occurs in response to the inhibition of PP5 expression, requires the p53 protein.

145 to three different TPR proteins as follows: PP5, FKBP52, and Hop.

146 PP5 forms a complex with ATR in a genotoxic stress-induc

147 We find that PP5 forms a stable 1:1 complex with Hsp70, but the inter

148 ssed proteins, namely protein phosphatase 5 (PP5), formyl peptide receptor 2, and annexin 1.

149 65% similarity with protein phosphatase 5's (PP5) from different species.

150 nd describes a novel potential substrate for PP5 function in vivo.

151 DNA3'pp5'G caps synthesized by the 3'-PO4/5'-OH ligase RtcB h

152 , RtcB catalyzes attack of the 5'-OH on DNA3'pp5'G to form a 3'-5' phosphodiester splice junction.

153 MP intermediate to a DNA 3'-PO4 to form DNA3'pp5'G.

154 O4 to form a "capped" 3' end structure, DNA3'pp5'G.

155 In addition, since the inhibition of PP5 gene expression has marked antiproliferative activit

156 udies suggest that compounds that inhibit of PP5 gene expression may be useful in the treatment of hu

157 To characterize the relationship of PP5, glucocorticoid receptor activation and p53, here we

158 an guanylylate the DNA 3'-PO4 to form a DNA3'pp5'GOH cap.

159 GR function in the following order: FKBP52 > PP5 > FKBP51.

160 ryation of phospho-tau by PP5 and found that PP5 had a K(m) of 8-13 microm toward tau, which is simil

161 ng the four C-terminal residues (496-499) of PP5 had no effect on its activity, but removing Gln-495

162 tein serine/threonine phosphatase designated PP5 has little basal activity, and physiological activat

163 PP5 has no apparent effect on the binding of hormone to

164 n non-neuronal cells, protein phosphatase 5 (PP5) has been found in complexes with heat shock protein

165 High levels of PP5 have been observed in human cancers, and constitutiv

166 e amount of p50(cdc37) associated with Hsp90/PP5-HRI heterocomplexes.

167 protein A, implicating a functional role for PP5 in a specific stage of the checkpoint signaling path

168 dence has implicated the protein phosphatase PP5 in a variety of signaling pathways.

169 lar complex comprising CXCR4, FAK, ASK1, and PP5 in ATII cells during wound healing.

170 r, our results showed 1) a critical role for PP5 in cytokine-induced resistance to GC-mediated eosino

171 To further characterize the role of PP5 in E(2)-regulated growth control, we constructed sta

172 ss the expression of the protein phosphatase PP5 in endobronchial biopsies and ASM cells.

173 Examination of roles for PP5 in fibroblasts generated from PP5-deficient embryos

174 ly conserved among species, and the roles of PP5 in normal tissues are not clear.

175 Overexpression of PP5 in PC12 cells resulted in dephosphorylation of tau a

176 Here, we identify PP5 in stable complexes with extracellular signal-regula

177 A comparable role for PP5 in the regulation of Chk1 phosphorylation was also o

178 Activation of PP5 in vitro by polyunsaturated fatty acids (e.g. arachi

179 onsible for the microtubular localization of PP5 in vivo.

180 Furthermore, depletion of endogenous PP5 increased cellular phospho-Ser 338 levels.

181 Loss of PP5 increased phosphorylation of GRalpha at serines 212

182 In addition, protein phosphatase-5 (PP5) increased its association with this heteromeric com

183 ptide repeat (TPR) of protein phosphatase 5 (PP5) increased PPARalpha or PPARbeta activity in a PPRE-

184 n of ASK-1, and studies with siRNA targeting PP5 indicate that PP5 acts to suppress the phosphorylati

185 nd P protein was reduced in rA2-PP2- and rA2-PP5-infected cells by 30 and 60%, respectively.

186 It also reveals that PP5 inhibition may antagonize estrogen-promoted events i

187 that the tetratricopeptide repeat domain of PP5 interacts specifically and directly with active Rac1

188 PP5 interacts with ATM in a DNA-damage-inducible manner.

189 wo-hybrid analysis and in vitro binding that PP5 interacts with CDC16 and CDC27, two subunits of the

190 Protein phosphatase 5 (PP5) interacts with MRK in a complex and dephosphorylate

191 Our results suggest that PP5 is a physiological regulator of Raf-1 signalling pat

192 PP5 is a serine/threonine phosphatase that also contains

193 lation on PP5 activity, and 3) revealed that PP5 is a target of the lipoxin A4-induced pathway counte

194 PP5 is a ubiquitously expressed Ser/Thr protein phosphat

195 In conclusion, PP5 is a unique phosphatase reciprocally regulating PPAR

196 The genetic disruption of PP5 is associated with enhanced and prolonged phosphoryl

197 The results suggest that PP5 is downstream of mTOR, and positively regulated by t

198 ors, such as cerebellar granule cells, where PP5 is either absent or below detection limits.

199 Like CKIepsilon, PP5 is expressed both in the master circadian clock in t

200 However, PP5 is highly conserved among species, and the roles of

201 If hypoxia is prolonged, the expression of PP5 is increased due to the activation of a transcriptio

202 nalysis suggests that the site of binding to PP5 is localized to the COOH-terminal block of tetratric

203 that the tetratricopeptide repeat domain of PP5 is required and sufficient for this interaction.

204 In cells exposed to UV irradiation, PP5 is required to elicit an appropriate S-phase checkpo

205 We report here that PP5 is strongly inhibited by micromolar concentrations o

206 PP5 is unique among protein phosphatases in that it cont

207 Protein phosphatase 5 (PP5) is auto-inhibited by intramolecular interactions wi

208 , we demonstrate that protein phosphatase 5 (PP5) is required for the ATR-mediated checkpoint activat

209 More importantly, after PP5 knockdown estrogen-promoted cell proliferation was s

210 ased in ASM cells from severe asthmatics and PP5 knockdown using siRNA restored fluticasone repressiv

211 to the cytoplasm, while GR in FKBP51 KO and PP5 KO cells showed a moderate shift to the nucleus, ind

212 riptional activity and lipid accumulation in PP5-KO cells pointing to Ser-112 as an important residue

213 In contrast, PPARgamma in PP5-KO cells was hyperphosphorylated at serine 112 but h

214 In response to adipogenic stimuli, PP5-KO mouse embryonic fibroblast cells showed almost no

215 rence with the expression or the activity of PP5 leads to impairment of the ATR-mediated phosphorylat

216 In addition, loss of PP5 leads to premature mitosis after hydroxyurea treatme

217 Thus, although critical for cell growth, PP5 likely acts either downstream or independently of c-

218 ion, indirect immunofluorescence showed that PP5 localizes to the mitotic spindle apparatus.

219 halamus-pituitary-adrenal axis suggests that PP5 may be an important modulator of glucocorticoid rece

220 tructure-based mutations in vivo reveal that PP5-mediated dephosphorylation is required for kinase an

221 The PP5-mediated dephosphorylation of Ser 338 inhibited Raf-

222 PP5-mediated dephosphorylation of the cochaperone Cdc37

223 ch normally stimulates K897 channels through PP5-mediated dephosphorylation, inhibits T897 channels t

224 om this structure we propose a mechanism for PP5-mediated hydrolysis of phosphoprotein substrates, wh

225 PP5(-/-) mouse embryonic fibroblasts demonstrated increa

226 blasts generated from PP5-deficient embryos (PP5(-/-) mouse embryonic fibroblasts) confirmed some kno

227 Expression of a catalytically inactive PP5 mutant inhibited the phosphorylation of ATM substrat

228 Expression of a dominant-negative PP5 mutant reduces PER phosphorylation by CKIepsilon in

229 our data show that hyper- or hypoactivity of PP5 mutants increases Hsp90 binding to its inhibitor, su

230 phosphorylation by modulating the effect of PP5 on CKIepsilon.

231 our TPR proteins (FKBP52, FKBP51, Cyp40, and PP5) on hormone-binding function of glucocorticoid recep

232 mycin did not affect either protein level of PP5 or association of PP5 with ASK1.

233 on HSP90 binding to PP5 but does not require PP5 or ERK1/2 activity.

234 and retains an inactive conformation, bound PP5 or stimulated its activity.

235 n detectable amounts of Hop, FKBP51, FKBP52, PP5, or p23, all co-chaperones found in hsp90 complexes

236 thought to mediate fatty acid activation of PP5, our data suggest that Asn-491, near its C-terminus,

237 observed in human cancers, and constitutive PP5 overexpression aids tumor progression in mouse model

238 asma membrane in intact cells and stimulated PP5 phosphatase activity in vitro.

239 Mice deficient in PP5 phosphatase have increased osteoblast numbers and hi

240 Taken together, our results suggest that PP5 plays a critical role in the ATR-mediated checkpoint

241 Together our findings indicate that PP5 plays an essential role in the activation and checkp

242 Together, these studies indicate that PP5 plays an important role in the survival of cells in

243 Serine/threonine protein phosphatase 5 (PP5, PPP5C) is known to interact with the chaperonin hea

244 We show that Cdc37 and PP5/Ppt1 associate in Hsp90 complexes in yeast and in hu

245 in yeast and in human tumor cells, and that PP5/Ppt1 regulates phosphorylation of Ser13-Cdc37 in viv

246 he chaperone-targeted protein phosphatase 5 (PP5/Ppt1), which does not affect isolated Cdc37.

247 sically interact with protein phosphatase 5 (PP5), previously identified as a negative regulator of A

248 ER recognition element was identified in the PP5 promoter.

249 Solution NMR studies reveal that Hsc70 and PP5 proteins are dynamically independent in complex, tet

250 Here we show that protein phosphatase 5 (PP5) reciprocally regulates each receptor by targeting e

251 threonine phosphatase protein phosphatase 5 (PP5) regulates hormone- and stress-induced cellular sign

252 gnaling, but direct biochemical evidence for PP5 regulation by Rac1 is lacking.

253 on of P protein, because the majority of rA2-PP5 remained cell associated.

254 cells, rA2-PP2 and, to a greater extent, rA2-PP5, replicated poorly in HEp-2 cells.

255 Moreover, shRNA knockdown of PP5 results in cells refractory to rosiglitazone treatme

256 y CKIepsilon in vivo, and down-regulation of PP5 significantly reduces the amplitude of circadian cyc

257 Similar to PP5 small interfering RNA inhibition, pretreatment of eo

258 However, Hsp70 binding to PP5 stimulates higher phosphatase activity of PP5 than t

259 PP5 stimulation by Rac provides a unique molecular mecha

260 and test a specific molecular mechanism for PP5 stimulation by Rac-GTP.

261 utation of predicted contact residues in the PP5 tetratricopeptide repeat domain or within Rac1 also

262 P5 stimulates higher phosphatase activity of PP5 than the binding of Hsp90.

263 HRI is mediated through Hsp90, as mutants of PP5 that do not bind Hsp90 do not interact with HRI.

264 atase activity which suggests dual roles for PP5 that might link chaperone systems with signaling pat

265 , we identify a Ser/Thr protein phosphatase (PP5) that promotes cellular proliferation by inhibiting

266 Indeed, in the absence of PP5 the MSC lineage allocation is skewed toward osteobla

267 Hsp90 has been shown to bind PP5 to activate its phosphatase activity.

268 Specific binding of PP5 to activated Rac1 provides a direct mechanism by whi

269 ibroblast cells were used to show binding of PP5 to both GRalpha and PPARgamma.

270 This tethered binding is expected to allow PP5 to carry out multi-site dephosphorylation of Hsp70-b

271 so show that the published structures of the PP5 TPR domain and the TPR domain of p67, the Rac-bindin

272 Mutation of the PP5 TPR domain at two predicted contact points with Rac-

273 three methods to disrupt Hsp90 function (GA, PP5-TPR, CHIP) resulted in an alteration in PPARalpha or

274 In the presence of rosiglitazone, PP5 translocates to the nucleus, binds to PPARgamma and

275 Consequently, activation of Rac1 promoted PP5 translocation to the plasma membrane in intact cells

276 y, we find that both Hsp90 and Hsp70 bind to PP5 using a luciferase fragment complementation assay.

277 The structure reveals PP5 utilization of conserved elements of phosphoprotein

278 0 is also known to bind to the TPR domain of PP5 via its C-terminal domain (C90), we investigated its

279 In addition, rA2-PP5 was also more attenuated than rA2-PP2 in replication

280 PP5 was also present in Hsp90 heterocomplexes with anoth

281 g shRNA in MLE-12 cells, but unaffected when PP5 was depleted.

282 The activity but not the protein level of PP5 was found to be decreased by approximately 20% in AD

283 PP5 was not thought to interact with partners homologous

284 MCF-7 cell lines in which the expression of PP5 was placed under the control of tetracycline-regulat

285 Protein phosphatase 5 (PP5) was identified as an inactivator that associates wi

286 Levels of PP5 were increased in ASM cells from severe asthmatics a

287 ifferences caused by the total disruption of PP5 were minor, suggesting that small molecule inhibitor

288 lation sites (S116L/S117R/S119L/S232A/S237A [PP5]) were introduced into the infectious RSV A2 strain.

289 serine/threonine protein phosphatase type 5 (PP5), which acts to turn off ASK-1/MKK-4/JNK signaling v

290 by the TPR domain of protein phosphatase 5 (PP5), which binds to the C terminus of the chaperone pro

291 creases expression of protein phosphatase 5 (PP5), which mediates the dephosphorylation of GR at Ser-

292 suggesting that small molecule inhibitors of PP5 will not have widespread systemic toxicity.

293 ia facilitates the association of endogenous PP5 with ASK-1.

294 ither protein level of PP5 or association of PP5 with ASK1.

295 but selectively decreases the interaction of PP5 with ERK2, in a manner that is independent of PP5 an

296 The interaction of PP5 with HRI is mediated through Hsp90, as mutants of PP

297 unctional significance of the interaction of PP5 with Hsp90-HRI heterocomplexes was examined by chara

298 Inhibition of PP5 with the microbial toxin, okadaic acid, blocked chan

299 on removing the C-terminal 13 amino acids of PP5, with a concomitant 50% decrease in arachidonic acid

300 expression of a toxin-insensitive mutant of PP5, Y451A, which we engineered.