ライフサイエンスコーパス: PKD

1 PKD and Gbetagamma inhibitors also attenuated protease-e

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

3 PKD is activated by recruitment to membranes containing

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

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

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

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

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

9 particles, and upon oral administration to a PKD murine model (Pkd1(fl/fl);Pax8-rtTA;Tet-O cre), a lo

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

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

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

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

14 esents a promising therapeutic agent against PKDs.

15 using glucose analogs ameliorates aggressive PKD in preclinical models.

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

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

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

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

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

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

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

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

24 est its utility for chronic diseases such as PKD, we loaded the candidate PKD drug, metformin, into c

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

26 iseases such as PKD, we loaded the candidate PKD drug, metformin, into chitosan nanoparticles, and up

27 Challenging PKD rat models with CaOx crystal deposition, or inducing

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

29 c relationship between ADPKD and ciliopathic PKD is not known.

30 genesis in the Tulp3 conditional ciliopathic PKD model.

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

32 Constitutive PKD activation in mouse C2C12 myogenic cells regulated m

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

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

35 n, cAMP formation, and PKA/protein kinase D (PKD) activation, but not beta-arrestin recruitment or PA

36 diacylglycerol (DAG), and protein kinase D (PKD) activity, activated or inhibited plasma membrane-lo

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

38 rmation, and activation of protein kinase D (PKD) and PKA, but not beta-arrestin recruitment or PAR(2

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

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

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

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

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

44 2)-dependent activation of protein kinase D (PKD) in the Golgi of HEK293 cells, in which PKD regulate

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

46 Protein kinase D (PKD) is an essential Ser/Thr kinase in animals and contr

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

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

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

50 Expression of Protein Kinase D (PKD), a negative regulator of SINGD, is reduced in diabe

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

52 2.6%) in the activation of protein kinase D (PKD), an alternate HDAC5 kinase.

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

54 Pyruvate kinase deficiency (PKD) is an autosomal-recessive enzyme defect of the glyc

55 Xbp1 pathway or cause polycystin-1-dependent PKD.

56 an efficient vertebrate model for developing PKD therapeutic strategies.

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

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

59 the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike r

60 mal-dominant (AD) polycystic kidney disease (PKD) exhibits high intra-familial variability suggesting

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

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

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

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

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

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

67 t, we generated 2 polycystic kidney disease (PKD) mouse models: kidney-specific Pkd1 knockout mice an

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

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

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

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

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

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

74 diseases such as polycystic kidney disease (PKD), the most common hereditary disease worldwide in wh

75 he development of polycystic kidney disease (PKD).

76 st enlargement in polycystic kidney disease (PKD).

77 utosomal dominant polycystic kidney disease (PKD).

78 f cystogenesis in polycystic kidney disease (PKD).

79 elevated cAMP in polycystic kidney disease (PKD).

80 pancreas features polycystic kidney disease (PKD).

81 cystin-1-mediated polycystic kidney disease (PKD).

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

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

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

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

86 ellular, phosphorylated pseudokinase domain (PKD) critical for activation of the C-terminal cGMP-synt

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

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 amples from patients with autosomal dominant PKD, embryonic kidney cultures, and an MDCK in vitro cys

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

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

93 PRRT2 were performed on patients from eight PKD families.

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

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

96 promotes disease progression in experimental PKD.

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

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

99 -null PKD mice compared with AQP3-expressing PKD mice, with the difference seen mainly in collecting

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

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

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

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

104 We therefore propose a new model for PKD activation in which the production of DAG leads to t

105 monstrates a novel, oral nanoformulation for PKD.

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

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

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

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

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

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

112 some biogenesis, with implications for human PKD.

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

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

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

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

117 owever, mechanisms for channel activation in PKD remain obscure.

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

119 utic approaches to delay cyst development in PKD.

120 ways involved in cyst growth and fibrosis in PKD.

121 his complex contributes to cyst formation in PKD.

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

123 therapeutic approach to slow cyst growth in PKD.

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

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

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

127 used on future directions and innovations in PKD research.

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

129 ole of nutrition and dietary manipulation in PKD.

130 ling a critical role for microenvironment in PKD.

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

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

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

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

135 teins and increased superoxide production in PKD patient-derived renal epithelial cells.

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

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

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

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

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

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

142 nt negative effect of catalytically inactive PKDs.

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

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

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

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

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

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

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

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

157 in human in vitro ADPKD models and multiple PKD mouse models after subcutaneous administration.

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

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

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

169 exes were significantly reduced in AQP3-null PKD mice compared with AQP3-expressing PKD mice, with th

170 on of DAG leads to the local accumulation of PKD at the membrane, which drives ULD-mediated dimerizat

171 Pharmacological activation of PKD counters SINGD and delays the onset of T2D.

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

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

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

175 led to rapid tubule dilation, activation of PKD-associated signaling pathways, and hypertrophy in tu

176 ein) prevented PAR2-stimulated activation of PKD.

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

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

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

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

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

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

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

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

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

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

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

188 We further show that the kinase domain of PKD dimerizes in a concentration-dependent manner and au

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

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

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

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

193 ndings of PKA facilitation and inhibition of PKD activation.

194 Conversely, inhibition of PKD exacerbates SINGD, mitigates insulin secretion and a

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

196 Inhibitors of PKD, Gbetagamma, and protein translation inhibited recov

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

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

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

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

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

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

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

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

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

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

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

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

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

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

214 novirus (HRV) induced the phosphorylation of PKD.

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

216 (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study

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

218 ch has been implicated in the progression of PKD.

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

220 -6 are required for environmental release of PKD-2::GFP-containing ECVs.

221 phatics that may also affect the severity of PKD.

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

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

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

225 he Consortium of Radiologic Imaging Study of PKD Study.

226 specificity and subcellular distribution of PKDs.

227 ties of the regulatory and kinase domains of PKDs.

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

229 , we determined the effect of 4E-BP1F113A on PKD.

230 argement of dendritic spines is dependent on PKD activity.

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

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

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

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

235 sation to the cilium is necessary to prevent PKD.

236 ted dimerization in cells but also prevented PKD activation loop phosphorylation upon DAG production.

237 ce of ciliary PC2 localisation in preventing PKD are limited because PC2 function is ablated througho

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

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

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

241 exhibiting phenotypes of rapidly progressive PKD and early lethality resembling classic ARPKD.

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

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

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

245 of cyst formation but never triggered rapid PKD.

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

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

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

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

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

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

252 cysts, leading to the progression of severe PKD.

253 their relevance is questioned in the simple PKDs.

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

255 by canonical and biased mechanisms stimulate PKD in the Golgi; PAR(2) mobilization and de novo synthe

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

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

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

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

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

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

262 We also provide evidence that PKD is expressed at concentrations 2 orders of magnitude

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

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

265 These results suggest that PKD progression may be accelerated by commonly occurring

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

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

268 he proteases stimulated translocation of the PKD activator Gbetagamma to the Golgi, coinciding with P

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

270 Here, we report the crystal structure of the PKD N terminus at 2.2 angstrom resolution containing a p

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

272 consistent with ATP binding stabilizing the PKD in a conformation analogous to that of catalytically

273 GC-B, we investigated how ATP binding to the PKD influenced guanylyl cyclase activity.

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

275 he catalytic aspartate, are conserved in the PKDs of GC-A and GC-B.

276 c mechanisms evolutionarily conserved in the PKDs promote the catalytic activation of transmembrane g

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

278 nzyme phosphate content, consistent with the PKDs lacking kinase activity.

279 ed regulatory or catalytic spines within the PKDs increased guanylyl cyclase activity, increased sens

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

281 rimary cilia have been considered central to PKD pathogenesis due to protein localization and common

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

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

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

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

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

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

288 ithelial cells to GPCR agonists that act via PKD.

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

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

291 (PKD) in the Golgi of HEK293 cells, in which PKD regulates protein trafficking.

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

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

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

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

296 he diagnosis and management of patients with PKD can be challenging due to difficulties in the diagno

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

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

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

300 neous inactivation of Xbp1 and Sec63 worsens PKD in this model.