ライフサイエンスコーパス: PKD

1 PKD is a family of three serine/threonine kinases (PKD-1

2 PKD phosphorylation, indicative of the activated state,

3 PKD prevalence in the sampled sites for both young-of-th

4 PKDs have a critical role in cell motility, migration an

5 ation induced translocation of Gbetagamma, a PKD activator, to the Golgi apparatus, determined by bio

6 of the actin binding protein cortactin in a PKD-dependent manner.

7 Furthermore, systemic administration of a PKD inhibitor protects d-galactosamine-sensitized mice f

8 ts trypsin and 2-furoyl-LIGRLO-NH2 activated PKD in the Golgi apparatus, where PKD regulates protein

9 ionally, in vivo stab wound injury activates PKD and induces COX-2 and other inflammatory genes in WT

10 Additional PKD variation(s) (inherited from the unaffected parent w

11 giogenesis, in vitro and in vivo, addressing PKD isoform specificity as a major factor for future the

12 esents a promising therapeutic agent against PKDs.

13 using glucose analogs ameliorates aggressive PKD in preclinical models.

14 Although PKD is broadly expressed and involved in numerous cellul

15 containing GFP-tagged polycystins LOV-1 and PKD-2.

16 activated in cyst-lining cells in ADPKD and PKD mouse models and may drive renal cyst growth, but th

17 bition of clathrin-mediated endocytosis, and PKD inhibitors do not need to be present during viral up

18 ed similarly in mice lacking the Rho-GEF and PKD-binding domains and wild-type controls.

19 owever, the requirements for the Rho-GEF and PKD-binding domains during development and cardiac hyper

20 Additionally, the AKAP13 Rho-GEF and PKD-binding domains mediate cardiomyocyte hypertrophy in

21 These results indicate that the Rho-GEF and PKD-binding domains of AKAP13 are not required for mouse

22 e spectrum of genetic causes for both HI and PKD and provide insights into gene regulation and PMM2 p

23 sed PC1, PC2, and FPC at similar levels, and PKD and control iPS cells exhibited comparable rates of

24 The polycystin proteins (PC and PKD), identified in linkage studies of polycystic kidney

25 g protein (mAKAP), along with PKCepsilon and PKD, localizes these components at or near the nuclear e

26 ves the activation of nPKCs (PKCepsilon) and PKD that can be abrogated by selective inhibitors or by

27 re substrates for protein kinase D (PKD) and PKD is known to be involved in the control of Golgi memb

28 y 92 cluster inhibits cyst proliferation and PKD progression in four orthologous, including two long-

29 The discovery of interaction between YAP and PKD pathways identifies a novel cross-talk in signal tra

30 oforms is deregulated in various tumours and PKDs, in particular PKD2, have been implicated in the re

31 te (cAMP), when added, induces cysts in both PKD organoids and controls.

32 udin-1 knockdown prevented TEER elevation by PKD inhibition or silencing in airway epithelial monolay

33 Yet within certain PKD families, striking differences in disease severity e

34 rastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of the kines

35 l test our hypothesis that compartmentalized PKD signaling reconciles disparate findings of PKA facil

36 Constitutive PKD activation in mouse C2C12 myogenic cells regulated m

37 e importance of PCP signaling for cystogenic PKD phenotypes has not been examined.

38 ding sites for protein kinase A (PKA) and D (PKD) and an active Rho-guanine nucleotide exchange facto

39 are required for long term protein kinase D (PKD) activation and subsequent induction of inflammatory

40 luated the contribution of protein kinase D (PKD) and Gbetagamma to this process.

41 d PI4KB are substrates for protein kinase D (PKD) and PKD is known to be involved in the control of G

42 eir cellular localization, Protein Kinase D (PKD) enzymes regulate different processes including Golg

43 ment of the cells with the protein kinase D (PKD) family inhibitors CRT0066101 and kb NB 142-70 preve

44 G-proteins (ARFs) and the protein kinase D (PKD) family of serine/threonine kinases.

45 In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via mu

46 ere pretreated or not with protein kinase D (PKD) inhibitors.

47 Protein kinase D (PKD) is a family of stress-responsive serine/threonine k

48 Protein kinase D (PKD) is known to be involved in Golgi-to-cell surface tr

49 Protein kinase D (PKD) isoforms are involved in controlling tumor cell mot

50 Protein kinase D (PKD) isoforms are protein kinase C effectors in signalin

51 analysis showed downstream protein kinase D (PKD) phosphorylation and phosphatase activation are asso

52 present study we show that protein kinase D (PKD) plays an important role in the formation and integr

53 i interact at the level of protein kinase D (PKD), a nodal point in cardiac hypertrophic signaling, r

54 2.6%) in the activation of protein kinase D (PKD), an alternate HDAC5 kinase.

55 n, sustained activation of protein kinase D (PKD), and nuclear translocation of NF-kappaB.

56 and activation of nuclear protein kinase D (PKD).

57 e investigated the role of protein kinase D (PKD)1 in the proinflammatory responses to GBS.

58 an efficient vertebrate model for developing PKD therapeutic strategies.

59 -talk between the polycystic kidney disease (PKD) and tuberous sclerosis complex (TSC) genes.

60 I) and congenital polycystic kidney disease (PKD) are rare, genetically heterogeneous disorders.

61 P) drives genetic polycystic kidney disease (PKD) cystogenesis.

62 of the downstream polycystic kidney disease (PKD) domain into a melanosomal core matrix.

63 n associated with polycystic kidney disease (PKD) genes, the majority of which encode proteins that l

64 Polycystic kidney disease (PKD) is a leading cause of ESRD worldwide.

65 Polycystic kidney disease (PKD) is a life-threatening disorder, commonly caused by

66 Proliferative kidney disease (PKD) is a major threat to wild and farmed salmonid popul

67 Polycystic kidney disease (PKD) is one of the most common life-threatening genetic

68 similar to known polycystic kidney disease (PKD) models.

69 cystin (TRPP) and polycystic kidney disease (PKD) proteins, play key roles in coupling extracellular

70 he second Ig-like polycystic kidney disease (PKD) repeat domain (PKD2) present in the ectodomain of A

71 utosomal dominant polycystic kidney disease (PKD), and ciliary-EV interactions have been proposed to

72 st common form of polycystic kidney disease (PKD), is a disorder with characteristics of neoplasia.

73 In polycystic kidney disease (PKD), renal parenchyma is destroyed by cysts, hypothesiz

74 Polycystic kidney disease (PKD), the most common genetic cause of chronic kidney fa

75 he development of polycystic kidney disease (PKD).

76 utosomal dominant polycystic kidney disease (PKD).

77 f cystogenesis in polycystic kidney disease (PKD).

78 elevated cAMP in polycystic kidney disease (PKD).

79 pancreas features polycystic kidney disease (PKD).

80 Polycystic kidney diseases (PKD) are genetic disorders characterized by progressive

81 Polycystic kidney diseases (PKDs) are genetic disorders that can cause renal failure

82 Polycystic kidney diseases (PKDs) comprise a subgroup of ciliopathies characterized

83 ily through the first, most membrane-distal, PKD domain (PKD1) of AAVR to promote transduction.

84 PC2), respectively, cause autosomal dominant PKD (ADPKD), whereas mutations in PKHD1, which encodes f

85 beings, and patients with autosomal dominant PKD (ADPKD); and (2) hepatorenal cystogenesis in vivo in

86 use of mTOR inhibitors in autosomal dominant PKD caused by hypomorphic or missense PKD1 mutations.

87 sts have been reported in autosomal dominant PKD fetal kidneys.

88 In early-stage autosomal dominant PKD kidneys, 50% of glomeruli were atubular or attached

89 ogressive PKD), and human autosomal dominant PKD were examined in early and late stages.

90 Paroxysmal kinesigenic dyskinesia (PKD) is characterized by recurrent and brief attacks of

91 s (BFIS), paroxysmal kinesigenic dyskinesia (PKD), and their combination-known as infantile convulsio

92 PRRT2 were performed on patients from eight PKD families.

93 genetic screen for regulators of C. elegans PKD-2 ciliary localization, we identified CIL-7, a myris

94 and the prototypical Caenorhabditis elegans PKD, DKF-2A, are exclusively (homo- or hetero-) dimers i

95 promotes disease progression in experimental PKD.

96 Potentially, broadly co-expressed PKD polypeptides may interact to generate homo- or heter

97 n AQP1-null PKD mice than in AQP1-expressing PKD mice, with the difference mainly attributed to a gre

98 NF1B, and PKHD1 associated with the familial PKD mutation in early ADPKD, these four genes were scree

99 For PKD recipients, we compared overall cancer risk with tha

100 novel dimerization domain are essential for PKD-mediated regulation of a key aspect of cell physiolo

101 represents a major technical improvement for PKD genotyping from trace amounts of DNA.

102 Our results reveal a major role for PKD and Gbetagamma in agonist-evoked mobilization of int

103 way of mTOR, as a new therapeutic target for PKD.

104 ggest that PDE1A is a viable drug target for PKD.

105 ation there is still no approved therapy for PKD in the United States.

106 f cyst formation is determined by functional PKD protein levels and the biologic context.

107 ing 8-Br-cAMP as a chemical to mimic genetic PKD and the glucocorticoid dexamethasone as the environm

108 However, PKD recipients were older (median age at transplantation

109 some biogenesis, with implications for human PKD.

110 Remarkably, we observed that the three human PKD isoforms display very different degrees of P + 1 loo

111 Consequently, impaired PKD functions attenuate activity-dependent changes in hi

112 In PKD, excessive cell proliferation and fluid secretion, p

113 isoforms could mediate cAMP accumulation in PKD, and identification of a specific pathogenic AC isof

114 The role of TGF-beta in PKD is not clearly understood, but nuclear accumulation

115 ways involved in cyst growth and fibrosis in PKD.

116 his complex contributes to cyst formation in PKD.

117 brosis, and the decline in renal function in PKD mice.

118 therapeutic approach to slow cyst growth in PKD.

119 The unadjusted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01

120 Cancer incidence in PKD recipients was 1233.6 per 100,000 person-years, 48%

121 We also compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poi

122 used on future directions and innovations in PKD research.

123 le adjustment, cancer incidence was lower in PKD recipients than in others (IRR, 0.84; 95% CI, 0.77 t

124 ole of nutrition and dietary manipulation in PKD.

125 ling a critical role for microenvironment in PKD.

126 Dysregulated miRNA expression is observed in PKD, but whether miRNAs are directly involved in kidney

127 To determine whether this process occurs in PKD, kidneys from pcy mice (moderately progressive PKD),

128 ted "AKI" pathways may drive pathogenesis in PKD.

129 int to activin signaling as a key pathway in PKD and a promising target for therapy.

130 cAMP signaling, a key pathogenic pathway in PKD, transactivated miR-21 promoter in kidney cells and

131 unique hypothesis for disease progression in PKD involving miRNAs and regulation of PKD gene dosage.

132 ily activated by Ca(2+), which is reduced in PKD cells.

133 ctivation (postnatal days 25-28) resulted in PKD developing in months.

134 ostnatal days 11 and 12) of Pkd1 resulted in PKD developing within weeks, whereas late inactivation (

135 The reason for the lower cancer risk in PKD recipients is not known but may relate to biologic c

136 approximately 92 as a therapeutic target in PKD.

137 mTOR signalling is upregulated in PKD and rapamycin slows cyst expansion, whereas renal in

138 he mechanisms of how c-Myc is upregulated in PKD but also suggests that targeting Brd4 with JQ1 may f

139 nt negative effect of catalytically inactive PKDs.

140 sters, which could be explained by increased PKD-related signaling in not only cystic epithelial cell

141 Knockdown of individual PKD isoforms in human KCs revealed contrasting growth re

142 itution of S427 likewise impedes GqR-induced PKD translocation and activation.

143 irway epithelial barrier disruption involves PKD-dependent actin cytoskeletal remodeling, possibly de

144 In polycystic liver (PLD) and kidney (PKD) diseases, increased cyclic adenosine monophosphate

145 a family of three serine/threonine kinases (PKD-1, -2, and -3) involved in the regulation of diverse

146 ECVs isolated from klp-6 animals and lacking PKD-2::GFP do not.

147 have discrete interactions with the Ig-like PKD domains of AAVR.

148 n this study, we found that PKD2 is the main PKD isoform expressed in osteoclastic cells.

149 Here, we demonstrate that mammalian PKDs 1-3 and the prototypical Caenorhabditis elegans PKD

150 nuclear signaling and inhibits GqR-mediated PKD activation by preventing its intracellular transloca

151 tumour growth and angiogenesis by mediating PKD-induced vascular endothelial growth factor secretion

152 (KspCre) results in aggressive or very mild PKD, respectively.

153 The phenotype was mild PKD and variable, including severe, PLD.

154 which result in significant PLD with minimal PKD.

155 To model PKD in human cells, we established induced pluripotent s

156 find that, contrary to the prevailing model, PKD mutations do not disrupt PCP signaling but instead a

157 Moreover, PKD inhibitors also block PV and FMDV replication.

158 tion of miR-21 is a common feature of murine PKD.

159 hromosome 3q in this PRRT2-mutation-negative PKD family.

160 plantation, 51 years versus 45 years for non-PKD recipients), and after multivariable adjustment, can

161 sted incidence was higher in PKD than in non-PKD recipients (IRR, 1.10; 95% CI, 1.01 to 1.20).

162 37 to 1.60), whereas cancer incidence in non-PKD recipients was 1119.1 per 100,000 person-years.

163 compared cancer incidence in PKD versus non-PKD renal transplant recipients using Poisson regression

164 ed ET-1-dependent PI4P depletion and nuclear PKD activation.

165 perinuclear Golgi PI4P depletion and nuclear PKD activation.

166 pe, and this complex is required for nuclear PKD activation.

167 envelope, to regulate activation of nuclear PKD and hypertrophic signaling pathways.

168 mber were significantly greater in AQP1-null PKD mice than in AQP1-expressing PKD mice, with the diff

169 creased beta-catenin expression in AQP1-null PKD mice, suggesting enhanced Wnt signaling.

170 C to the Golgi is required for activation of PKD in this compartment as well as for subsequent induct

171 GqR-induced translocation and activation of PKD throughout the cardiomyocyte.

172 signaling drives local nuclear activation of PKD, without preceding sarcolemmal translocation.

173 ein) prevented PAR2-stimulated activation of PKD.

174 potential new treatment for some aspects of PKD, with the possibility for synergy with current epith

175 We show that long-lasting attenuation of PKD in the juvenile cystic kidneys (jck) mouse model of

176 sed to play a central role in the biology of PKD.

177 utations, or possible novel genetic cause of PKD phenotypes.

178 -like kinase 5) in renal epithelial cells of PKD mice, which had little to no effect on the expressio

179 a underline the importance and complexity of PKD signaling in human epidermis and suggest a central r

180 vins have not been studied in the context of PKD.

181 Pde1b or Pde3b aggravated the development of PKD and was associated with higher levels of protein kin

182 PDE1C) and PDE3A modulate the development of PKD, possibly through the regulation of compartmentalize

183 Es may, therefore, retard the development of PKD.

184 Disruption of PKD dimerization abrogates secretion of PAUF, a protein

185 Expression of PKD isoforms is deregulated in various tumours and PKDs,

186 by expression of dominant-negative forms of PKD.

187 onstrate differential regulation/function of PKD isoforms under oxidative stress, but also have impli

188 awardees and their vision for the future of PKD research.

189 been shown to be a common causative gene of PKD.

190 ndings of PKA facilitation and inhibition of PKD activation.

191 Either inhibition of PKD activity or silencing of PKD increased transepitheli

192 further provide evidence that inhibition of PKD blocks mitotic Raf-1 and mitogen-activated protein k

193 Inhibitors of PKD (CRT0066101) and Gbetagamma (gallein) prevented PAR2

194 The localization of PKD within cells is mediated by interaction with differe

195 Loss of PKD activity reduced expression of DC-STAMP in RANKL-sti

196 ic cells, as a new and important mediator of PKD progression.

197 erials establish a highly efficient model of PKD cystogenesis that directly implicates the microenvir

198 miR-17 approximately 92 in a mouse model of PKD retards kidney cyst growth, improves renal function,

199 stigated the role of AC6 in a mouse model of PKD that is homozygous for the loxP-flanked PKD1 gene an

200 iously, we have generated a genetic model of PKD using human pluripotent stem cells and derived kidne

201 CD1-pcy/pcy mice, a juvenile model of PKD, daily treated with 13 [Formula: see text]g of mamba

202 yst formation and renal injury in a model of PKD.

203 has been upregulated in all rodent models of PKD and ADPKD patients with unknown mechanism.

204 pathogenic role of miRNAs in mouse models of PKD and identify miR-17 approximately 92 as a therapeuti

205 cluster, is up-regulated in mouse models of PKD.

206 formation in three distinct mouse models of PKD.

207 Specifically, the inference that mutation of PKD genes interferes with PCP signaling is untested, and

208 Removal of stroma enables outgrowth of PKD cell lines, which exhibit defects in PC1 expression

209 We further found that overexpression of PKD, in particular PKD3, markedly suppressed the mRNA an

210 ling pathways underlying the pathogenesis of PKD and considers the therapeutic relevance of treatment

211 tween these proteins and the pathogenesis of PKD remains unclear.

212 he most relevant PDEs in the pathogenesis of PKD, we examined cyst development in Pde1- or Pde3-knock

213 HRV infection induces the phosphorylation of PKD, and inhibitors of this kinase effectively block HRV

214 PKA-dependent phosphorylation of PKD-S427 fine-tunes the PKD responsiveness to GqR-agonis

215 to direct, PKA-dependent phosphorylation of PKD-S427.

216 novirus (HRV) induced the phosphorylation of PKD.

217 port on the spatial and temporal profiles of PKD activation using green fluorescent protein-tagged PK

218 (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study

219 eduction of cAMP levels slows progression of PKD, this finding has not led to an established safe and

220 f SMAD2/3 target genes or the progression of PKD.

221 ch has been implicated in the progression of PKD.

222 on in PKD involving miRNAs and regulation of PKD gene dosage.

223 -6 are required for environmental release of PKD-2::GFP-containing ECVs.

224 nd through posttranscriptional repression of PKD genes Pkd1, Pkd2, and hepatocyte nuclear factor-1bet

225 phatics that may also affect the severity of PKD.

226 r inhibition of PKD activity or silencing of PKD increased transepithelial electrical resistance (TEE

227 Simultaneous silencing of PKD isoforms resulted in a more pronounced proliferation

228 Consortium for Radiologic Imaging Study of PKD (CRISP) participants (n=173) were used for external

229 We carried out an integrated study of PKD in a prealpine Swiss river (the Wigger).

230 he Consortium of Radiologic Imaging Study of PKD Study.

231 ight be more beneficial for the treatment of PKD and PLD.

232 ein expression levels and support the use of PKD iPS cells for investigating disease pathophysiology.

233 specificity and subcellular distribution of PKDs.

234 ties of the regulatory and kinase domains of PKDs.

235 human KCs with pharmacological inhibitors of PKDs resulted in growth arrest.

236 argement of dendritic spines is dependent on PKD activity.

237 gehog signaling, features also seen in other PKD models.

238 ence in the expression and function of other PKD isoforms.

239 arget gene Ptpn13 also linked SMYD2 to other PKD-associated signaling pathways, including ERK, mTOR,

240 Our studies using pharmacological PKD inhibitors and PKD1-knockdown macrophages revealed t

241 contrast to the hypothesis that polycystin (PKD) channels initiate changes in ciliary calcium that a

242 ever, less than 50% of patients with primary PKD harbor mutations in PRRT2.

243 ing interferes with CE and/or OCD to produce PKD.

244 idneys from pcy mice (moderately progressive PKD), kidneys from cpk mice (rapidly progressive PKD), a

245 , kidneys from cpk mice (rapidly progressive PKD), and human autosomal dominant PKD were examined in

246 e life of pcy/pcy mice, a slowly progressive PKD model.

247 ne more than any other individual to promote PKD research around the world.

248 of cyst formation but never triggered rapid PKD.

249 /polyductin (FPC), cause autosomal recessive PKD (ARPKD).

250 and PCK rats (a model of autosomal recessive PKD [ARPKD]), healthy human beings, and patients with au

251 pk/cpk) mice, a model of autosomal recessive PKD, leading to a modest but significant increase in lif

252 mylases, only ttll-11 specifically regulates PKD-2 localization in EV-releasing neurons.

253 phalic sensory organ, and failure to release PKD-2::GFP-containing EVs to the environment.

254 , these data demonstrate that HSP27 requires PKD-mediated phosphorylation for its suppression of ASK1

255 d, producing cysts phenotypically resembling PKD that expand massively to 1-centimetre diameters.

256 Second, PKD inhibitors reduced HRV genome replication, protein e

257 preceded a rapid and massive onset of severe PKD that was remarkably similar to human ADPKD.

258 cysts, leading to the progression of severe PKD.

259 cance, and physiological relevance of stable PKD-PKD interactions are largely unknown.

260 PK1 has traditionally been used for studying PKD-causing mutations and Ca(2+) signaling in 2D culture

261 Thus, PLCepsilon links GPCRs to sustained PKD activation, providing a means for GPCR ligands that

262 ation using green fluorescent protein-tagged PKD (wildtype or mutant S427E) and targeted fluorescence

263 data show for the first time that targeting PKD with small molecules can inhibit the replication of

264 ates cyst growth in short-term and long-term PKD mouse models.

265 From these data, we conclude that PKD activity promotes differentiation of osteoclast prog

266 ter photobleaching analyses demonstrate that PKD is crucial for the cleavage of the noncompact zones

267 This is the first description that PKD may represent a target for antiviral drug discovery.

268 We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulat

269 We hypothesized that PKD cystogenesis is accentuated by an aberrant fetal mil

270 ar and lipid transport, we hypothesized that PKD played a role in viral replication.

271 These novel findings indicate that PKD negatively regulates human airway epithelial barrier

272 with the PKD inhibitor CID755673 showed that PKD activity is dispensable for induction of bone marrow

273 Our findings suggest that PKD controls interstack Golgi connections in a Raf-1/MEK

274 Here we identify a new interplay between the PKD and TSC genes, with important implications for the p

275 These results identify a novel role for the PKD family in the control of biphasic localization, phos

276 Protein kinase D2 (PKD2) is a member of the PKD family of serine/threonine kinases, a subfamily of t

277 at the ciliary-membrane translocation of the PKD proteins polycystin-1 and polycystin-2 is compromise

278 t phosphorylation of PKD-S427 fine-tunes the PKD responsiveness to GqR-agonists, serving as a key int

279 RNAi against PKD2 and treatment with the PKD inhibitor CID755673 showed that PKD activity is disp

280 d demonstrates, for the first time, that the PKDs feed into the YAP pathway.

281 ication of HRV, PV, and FMDV, and therefore, PKD may represent a novel antiviral target for drug disc

282 Among the three PKD isoforms, PKD3 knockdown was the most efficient one

283 Exposure to PKD or PKC family inhibitors did not prevent PKD1 phosph

284 Patients from the Mayo Clinic Translational PKD Center with ADPKD (n=590) with computed tomography/m

285 Polycystin complexes, or TRPP-PKD complexes, made of transient receptor potential chan

286 n the severe renal manifestations of the TSC/PKD contiguous gene syndrome and open new perspectives f

287 In 1 case, we recorded typical PKD spells by video-EEG-polygraphy, documenting a cortic

288 A major barrier to understanding PKD is the absence of human cellular models that accurat

289 Undifferentiated PKD iPS cells, control iPS cells, and embryonic stem cel

290 Pretreatment with two structurally unrelated PKD inhibitors markedly attenuated RSV-induced effects.

291 ithelial cells to GPCR agonists that act via PKD.

292 pendent, blocking HDAC5 phosphorylation when PKD was active engaged an alternative compensatory adapt

293 activated PKD in the Golgi apparatus, where PKD regulates protein trafficking.

294 tified the molecular mechanism through which PKD regulates viral replication, our data suggest that t

295 ormal glycosylation has been associated with PKD, and we found that deglycosylation in cultured pancr

296 of this study is to use eight families with PKD to identify the pathogenic PRRT2 mutations, or possi

297 Mice with PKD had increased expression of activin ligands, even at

298 study included 10,166 kidney recipients with PKD and 107,339 without PKD.

299 own whether renal transplant recipients with PKD have an increased risk of cancer.

300 dney recipients with PKD and 107,339 without PKD.