ライフサイエンスコーパス: PDK1

1 tivator phosphoinositide-dependent kinase-1 (PDK1).

2 s including pyruvate dehydrogenase kinase 1 (PDK1).

3 phosphoinositide-dependent protein kinase 1 (PDK1).

4 tion of phosphoinositide-dependent kinase 1 (PDK1).

5 phosphoinositide-dependent protein kinase 1 (PDK1).

6 characteristics by suppressing both H19 and PDK1.

7 375 and is associated with reduced levels of Pdk1.

8 s of Mir375 target messenger RNAs, including Pdk1.

9 ith the peptide docking motif for binding to PDK1.

10 ed in part by the PPARbeta/delta target gene PDK1.

11 ral compounds displayed high selectivity for PDK1.

12 sphorylated and its phosphorylation required Pdk1.

13 brane localization and signaling function of PDK1.

14 S473 and T308 phosphorylation by mTORC2 and PDK1.

15 uggesting a regulatory loop between CDK2 and PDK1.

16 he activity of the cell survival pathway via PDK1.

17 ne a key role for hBVR in Akt1 activation by PDK1.

18 mouse brain presented higher mRNA levels of PDK1-3 and PDH phosphorylation and decreased energy leve

19 PDK1 ablation enhanced cell cycle entry and apoptosis of

20 that the PDH flux is maintained by unchanged PDK1 abundance, despite the presence of HIF1.

21 In osteoblasts, PDK1 activated the CREB/CBP complex, which in turn contr

22 PDK1 activates AKT suggesting that PDK1 inhibition might

23 Some congeners displayed AC(50) values for PDK1 activation in the submicromolar range.

24 In addition, Pdk1 activation of the downstream effector p90RSK is als

25 osphorylation and activation by its upstream PDK1 activator.

26 as determined to be an important mediator of PDK1 activities in melanoma cells.

27 Furthermore, sphingolipid levels and PDK1 activity are also increased in hearts of FRDA patie

28 Attenuation of FAK, Src, PI3K, or PDK1 activity blocked YAP nuclear accumulation stimulate

29 ich is used for lipid-mediated regulation of PDK1 activity.

30 In addition, we showed that PDK1 aids the rescue of aPKC in in vitro rephosphorylati

31 dings illustrate the in vivo function of the PDK1-AKT-CREB/CBP pathway in bone formation and provide

32 pies targeting the aberrantly activated PI3K/PDK1/Akt pathway might be increased by the parallel bloc

33 The PI3K/PDK1/Akt signaling axis is centrally involved in cellula

34 ops have been identified that attenuate PI3K/PDK1/Akt-dependent signaling.

35 llin is capable of attenuating both the PI3K/PDK1/Akt/mTOR and the PKC/JNK/AP1 pathways.

36 We examined the role of hBVR in PDK1/Akt1/GSK3 signaling and Akt1 in hBVR phosphorylatio

37 rgeting phosphoinositide-dependent kinase 1 (PDK1) along with cisplatin, melphalan, camptothecin, or

38 PDK1 also was essential for the survival and activation

39 (IGF-1R), an upstream signaling molecule for PDK1, also correlated with fluctuations of PDK1/PCNA in

40 CDK2 knockdown also reduced expression of PDK1, an activator of the cell survival kinase Akt, and

41 Lon does not rapidly degrade PDK1 and -2, indicating specificity toward the PDK isofo

42 splayed a relative increase in the levels of PDK1 and activation of the AKT pathway.

43 On activation of the pathway, PDK1 and AKT1/2 translocate to the membrane and bind to

44 ide binding orientation in the PIF pocket of PDK1 and assessed subtle relationships between PIFtide p

45 RNAi-mediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased

46 However, PDK1 and GSK3beta contributed to the overall response to

47 Immunoprecipitation analysis showed that PDK1 and hBVR interact through hBVR's PDK1 binding (161)

48 cally with the pleckstrin homology domain of PDK1 and impairs formation of a PDK1/PLCgamma1 complex.

49 f a peptide docking motif (PIFtide) bound to PDK1 and mapped binding energy hot spots using mutationa

50 n epidermal growth factor (EGF) stimulation, PDK1 and MRCKalpha colocalize at the cell membrane in la

51 m of growth factor receptors and upstream of PDK1 and mTORC2 and copurifies with PI3K in immunoprecip

52 endent translation through activation of the PDK1 and mTORC2 kinases.

53 ferentiation is well documented, the role of PDK1 and other downstream effectors is underexplored.

54 nscriptional regulator encoded by o2 include pdk1 and pdk2 that specify pyruvate phosphate dikinase (

55 pdk1 and pdk2 were inactivated individually by transposo

56 o interfere with interaction of E2.E3BP with PDK1 and PDK3 is promising.

57 anced protein levels of PDH kinases 1 and 3 (PDK1 and PDK3).

58 K1[Ser(P)(422)] and C4-CER coincidently bind PDK1 and permit PDK1 to autophosphorylate at Ser(241).

59 ed AKTThr308 phosphorylation is dependent on PDK1 and PI3K but not EGF receptor or IGF1R.

60 e associated with differential activation of PDK1 and PKC-alpha.

61 pathways allows for convergent activation of PDK1 and protein kinase A during paired stimulation to i

62 ortantly, C4-CER-mediated activation of both PDK1 and SGK1 is independent of the PI3K/Akt/mammalian t

63 orylation and phosphorylation events between PDK1 and SGK1.

64 Genetic or pharmacologic inhibition of PDK1 and SGK3 attenuated melanoma growth by inducing G1

65 is, providing a rationale for targeting PI3K/PDK1 and TGFbeta signaling in advanced HNSCC patients wi

66 n induces the formation of a complex of AKT, PDK1 and the GRP78 chaperone protein, directing phosphor

67 residues, Thr(308) and Ser(473), mediated by PDK1 and the mammalian target of rapamycin complex 2 (mT

68 Whilst interaction with PDK1 and the mTORC2 complex component SIN1 was preserved

69 We show genetically that the PDK1 and TOR phosphorylation sites in Ypk1 as well as th

70 ession of the pyruvate dehydrogenase kinase (PDK1) and EGFR along with the hypoxia-inducing factor (H

71 3-phosphoinositide-dependent protein kinase (PDK1) and enhanced transforming growth factor beta (TGFb

72 pression of pyruvate dehydrogenase kinase 1 (PDK1) and lactate dehydrogenase A (LDHA).

73 phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2) to trigger ne

74 phosphoinositide dependent protein kinase-1 (Pdk1) and myocyte enhancer factor-2 (Mef2).

75 3K) and phosphoinositide-dependent kinase 1 (PDK1), and Dex induced translocation of PDK1 to endosome

76 321 acetylation inhibits PDHA1 by recruiting PDK1, and K202 acetylation inhibits PDP1 by dissociating

77 activity of upstream kinases including PI3K, PDK1, and mTORC2 as well as closely related kinases that

78 eby activating transcription of BNIP3, LDHA, PDK1, and SLC2A1, which encode proteins that are require

79 influx promoted p-Akt, an effect blocked by PDK1, and/or CaMKK2, siRNAs, and by PI3K and/or CaMKK in

80 Additionally, PDK1- and LDHA-overexpressing cells exhibited decreased

81 Therefore, PDK1 appears to contribute to HSC function partially via

82 B-cell progenitors lacking PDK1 arrested at the transition of pro-B to pre-B cells,

83 Our results reveal PDK1 as a central regulator of keratinocyte homeostasis

84 Collectively, our studies establish PDK1 as a key driver and candidate therapeutic target in

85 ork highlights the potential significance of PDK1 as a therapeutic target to improve melanoma treatme

86 phosphoinositide-dependent protein kinase 1 (PDK1) as a key modifier of ribociclib sensitivity in est

87 on of 3-phosphoinositide-dependent kinase 1 (PDK1) as a key regulator of CBP activity and demonstrate

88 We identify pyruvate dehydrogenase kinase 1 (PDK1) as an important direct target within a larger gene

89 ily, including AKT, PKC, and, most recently, PDK1, as elucidated recently in studies of Braf::Pten mu

90 PDK1 associates with the core Hippo pathway-kinase compl

91 becomes phosphorylated in vitro by purified PDK1 at the activation loop.

92 g the localization and activation of AKT and PDK1 at the membrane and driving PI3K signaling to a lev

93 ore, inhibition of the macrophage HIF-1alpha-PDK1 axis suppresses systemic inflammation, suggesting a

94 ethod to stratify patients with melanoma for PDK1-based therapies.

95 d that PDK1 and hBVR interact through hBVR's PDK1 binding (161)RFGFPAFS motif and formation of the PD

96 ue in cellular studies, the understanding of PDK1 biology, and the impact on the therapeutic potentia

97 cer cells resistant to PI3Kalpha inhibition, PDK1 blockade restores sensitivity to these therapies.

98 phosphoinositide-dependent protein kinase 1 (PDK1), both modulators of cellular metastasis targeted b

99 We then solved structures of PDK1 bound to the allosteric small molecules, which reve

100 PI3K) and phosphoinositide-dependent kinase (PDK1), but independent of AKT activity.

101 served allosteric site on the protein kinase PDK1 called the PDK1-interacting fragment (PIF)tide-bind

102 Lack of PDK1 caused HSCs to be less quiescent and to produce a h

103 The resultant mice (PDK1-CKO) spontaneously developed severe dermatitis, ski

104 PDK1 coimmunoprecipitated with PKCiota in cells without

105 PDK1 comigrated with the Rab11 compartment and, to some

106 Pharmacological inhibition of PDK1 completely reversed HIF1alpha-driven bone formation

107 Using a recently published PDK1 compound as a template, several new scaffolds that

108 Here, we report that PDK1 contributes functionally to skin pigmentation and t

109 SGK1, which is activated by PDK1, contributes to the maintenance of residual mTORC1

110 Through its regulation of AGC kinases, PDK1 controls many basic cellular processes, from transl

111 Phosphoinositide-dependent kinase-1 (PDK1) controls the activation of a subset of AGC kinases

112 PDK1 expression in hypoxia, and ablation of PDK1 counteracts H19-mediated glycolysis and self-renewa

113 se disulfide conjugation between PIFtide and PDK1 cysteine mutants, we defined the PIFtide binding or

114 Loss of PDK1 decreased the expression of the IgH chain in pro-B

115 PDK1-deficient HSCs also exhibited reduced ROS levels, a

116 e in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defe

117 PDK1-deficient HSCs were also unable to reconstitute the

118 hibited reduced ROS levels, and treatment of PDK1-deficient HSCs with L-butathioninesulfoximine in vi

119 PDK1-deficient keratinocytes exhibit intrinsic defects i

120 ce heterozygous for both osteoblast-specific Pdk1 deletion and either Runx2 or Creb deletion.

121 spectrum phenotypes with osteoblast-specific Pdk1 deletion in mice (Pdk1osx mice) and by the genetic

122 We found that PDK1 deletion strongly impaired B cell receptor (BCR) si

123 ificantly reduced or completely prevented by Pdk1 deletion.

124 Gene expression analyses identified Pdk1-dependent changes in FOXO3a-regulated genes, and in

125 iates in response to EGF signaling in a PI3K-PDK1-dependent manner, leading to inactivation of Lats,

126 O treatment, MOR activates PKCzeta through a PDK1-dependent signaling pathway to induce CCR5 phosphor

127 phosphoinositide-dependent protein kinase 1 (PDK1) directly correlated with PCNA levels.

128 elial cells and intestinal crypt enterocytes PDK1 distributes to an apical membrane compartment compr

129 found that immunohistochemical expression of PDK1, EGFR, and HIF-1alpha were elevated in glioblastoma

130 ediated attenuation of PDK1 and EGFR lowered PDK1-EGFR activation and decreased HIF-1alpha expression

131 Conversely, high levels of PDK1 enhance BCSC properties and are correlated with poo

132 In order to better understand PDK1 evolution within plants, we have isolated and chara

133 th Alzheimer disease exhibited a decrease in PDK1 expression compared with nondemented patients.

134 Accordingly, H19 and PDK1 expression exhibits strong correlations in primary

135 Furthermore, H19 knockdown decreases PDK1 expression in hypoxia, and ablation of PDK1 counter

136 our findings indicated that hypoxia-induced PDK1 expression may promote EGFR activation, initiating

137 PDK1 expression suffices for its activity, owing to auto

138 large cohorts of nevi and melanoma samples, PDK1 expression was significantly higher in primary mela

139 ells exhibit reduced PDH activity, increased PDK1 expression, and PDK inhibition partially rescues GL

140 NOX4, HIF-1alpha, and glycolytic enzyme and PDK1 expression, suggesting that DF leads to metabolic r

141 ble factor 1alpha, leading to an increase in PDK1 expression.

142 However, unlike PDK1 from other plants, the P. patens PDK1 protein does

143 nced the specific activity of the His-tagged PDK1 (full-length, and the truncated kinase domain) and

144 ding a unique opportunity to further dissect PDK1 function and predict the pharmacological consequenc

145 work has been done to understand the role of PDK1 function in cells, recently discovered potent and s

146 Collectively, we propose that PDK1 functions as a cellular sensor that balances basal

147 ants, we have isolated and characterized the PDK1 gene from the moss Physcomitrella patens (PpPDK1),

148 Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK

149 s demonstrate that the glycolysis gatekeeper PDK1 has a critical role in BCSC reprogramming and provi

150 However, while PDK1 has been investigated intensively as an oncology ta

151 ing (161)RFGFPAFS motif and formation of the PDK1/hBVR/Akt1 complex.

152 e potency of the best compounds to stabilize PDK1 in a thermal stability shift assay was in the same

153 poses by determining a crystal structure of PDK1 in complex with 4.

154 The crystal structure of PDK1 in complex with compound 4h revealed that additiona

155 argeting approaches to elucidate the role of PDK1 in early and peripheral B cell differentiation.

156 Using a conditional knockout of PDK1 in haematopoietic cells, we demonstrate that PDK1 i

157 However, the role of PDK1 in HSCs has not been fully defined.

158 backgrounds, we demonstrate that ablation of PDK1 in keratinocytes is the major driver of disease pat

159 osphingosine activates Mef2 activity through PDK1 in mammalian neuronal cell line suggesting that the

160 The physiological role of PDK1 in regulating skin and immune homeostasis is not kn

161 Selective inactivation of Pdk1 in the melanocytes of Braf(V600E)::Pten(-/-) or Bra

162 irect genetic evidence for the importance of PDK1, in part through FOXO3a-dependent pathway, in melan

163 We also noted that responsiveness to PDK1 inhibition associated with decreased expression of

164 d the impact on the therapeutic potential of PDK1 inhibition in cancer.

165 PDK1 activates AKT suggesting that PDK1 inhibition might suppress tumor development.

166 this study we present the results of in vivo PDK1 inhibition through a universally applicable RNAi ap

167 screen, pan-PI3K inhibition synergized with PDK1 inhibition to suppress melanoma growth, suggesting

168 predict the pharmacological consequences of PDK1 inhibition.

169 Administration of the PDK1 inhibitor GSK2334470 (PDKi) effectively delayed mel

170 ether a newly identified and highly specific PDK1 inhibitor, 2-O-benzyl-myo-inositol 1,3,4,5,6-pentak

171 the in vivo efficacies of AR-42 and AR-12, a PDK1 inhibitor, we generated and used luciferase-express

172 acquisition of conditioning is blocked by a PDK1 inhibitor.

173 ive reviews the discovery of these selective PDK1 inhibitors and highlights their value in cellular s

174 scovered potent and selective small molecule PDK1 inhibitors are providing a unique opportunity to fu

175 eric small molecules are substrate-selective PDK1 inhibitors when used as single agents, but when com

176 PDK1 knockdown and two different PDK1 inhibitors-BX-912 and a specific pseudosubstrate pe

177 enhance the anticancer activity of existing PDK1 inhibitors.

178 PDK1 inhibits Hippo signaling, leading to enhanced nucle

179 PDK1 inhibits pyruvate flux to mitochondrial respiration

180 c site on the protein kinase PDK1 called the PDK1-interacting fragment (PIF)tide-binding site, or PIF

181 PDK1 is a HIF-1-regulated gene and our findings indicate

182 In mouse xenograft tumor, PDK1 is accumulated in hypoxic regions and activates gly

183 Here we developed a mouse model in which PDK1 is conditionally ablated in activated CD4 T cells,

184 in haematopoietic cells, we demonstrate that PDK1 is essential for B cell development.

185 In summary, our results demonstrate that PDK1 is indispensable for B cell survival, proliferation

186 e, to the pleckstrin homology (PH) domain of PDK1 is known to be essential for its interaction with a

187 f downstream kinases, the mechanism by which PDK1 is recruited to the plasma membrane remains controv

188 PDK1 is responsible for regulating the activity of relat

189 phosphoinositide-dependent protein kinase 1 (PDK1) is a highly conserved eukaryotic kinase that is a

190 Phosphoinositide-dependent kinase-1 (PDK1) is a key signaling molecule downstream of the phos

191 Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-k

192 Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein target that has generated considerabl

193 Phosphoinositide-dependent kinase-1 (PDK1) is a serine/threonine protein kinase that phosphor

194 3-Phosphoinositide-dependent kinase-1 (PDK1) is a ubiquitously expressed serine/threonine kinas

195 e show that pyruvate dehydrogenase kinase 1 (PDK1) is enriched in breast cancer stem cells (BCSCs), w

196 ted 3-phosphoinositide-dependent kinase-1 (p-PDK1) is increased in response to paired and decreased i

197 phosphoinositide-dependent protein kinase 1 (PDK1) is the activating kinase for newly synthesized mol

198 Phosphoinositide-dependent protein kinase-1 (PDK1) is the pivotal node in the PI3K pathway, regulatin

199 Using CD8(+) T cells from pdk1(K465E/K465E) knockin mice, we found that decreased

200 Treatment of cells with PKC, PKA, and PDK1 kinase activators increased activity, whereas inhib

201 are was used to discover a potent allosteric PDK1 kinase modulator.

202 PDK1 knockdown and two different PDK1 inhibitors-BX-912

203 Combined CaMKK2 and PDK1 knockdown or CaMKK and PI3K inhibition, respectivel

204 8 and Ser-473 to extents similar to those of PDK1 knockdown or PI3K inhibition.

205 Furthermore, PDK1 knockdown reduced the expression of CDK2 suggesting

206 Thus, despite efficient PDK1 knockdown, inhibition of the PI3K pathway was margi

207 that it can functionally complement a yeast PDK1 knockout line.

208 As a result, Ccnd3 is upregulated in PDK1 knockout pre-B cells and they have an impaired abil

209 uction of both Pax5 and Bcl2A1 together into PDK1 knockout pro-B cells restored their ability to diff

210 sion of Pax5 in pre-B cells was decreased in PDK1 knockouts, which correlated with reduced expression

211 Finally, RNAi-mediated knockdown of PDK1 led to a reduction in PCNA expression and cell prol

212 y associated with expression of GLUT1, LDHA, PDK1, LOX, LOXL2, and L1CAM mRNA in human breast cancer

213 transporter 1, and glycolytic genes, hk1 and pdk1, lung fluorine-18-labeled 2-fluoro-2-deoxyglucose l

214 kinases phosphoinositide-dependent kinase 1 (PDK1), mammalian target of rapamycin (mTor), and protein

215 ross kingdoms, it is not well understood how PDK1 may have evolved within kingdoms.

216 1 proteins suggests that lipid regulation of PDK1 may not commonly occur in algae and nonvascular lan

217 we discovered a functional pathway involving PDK1-mediated activation of MRCKalpha, which links EGF s

218 T S473 phosphorylation without affecting the PDK1-mediated AKT T308 phosphorylation or TORC1 activity

219 Here we show that HIF-1alpha-PDK1-mediated metabolic changes occur in mild hypoxia, w

220 r results indicate that an iron/sphingolipid/Pdk1/Mef2 pathway may play a role in FRDA.

221 in mice also activates an iron/sphingolipid/PDK1/Mef2 pathway, indicating that the mechanism is evol

222 stored proliferation and colony formation of Pdk1(-/-) melanoma cells.

223 Pdk1(-/-) melanomas exhibit a marked decrease in the act

224 of its substrate Akt-p, together with PI3K, PDK1, mTOR (mammalian target of rapamycin), and p70S6K,

225 The pdk1- mutation is seedling-lethal, indicating that C4 ph

226 We show that the effect of PDK1 on cell migration does not involve its kinase activ

227 sphorylates pyruvate dehydrogenase kinase 1 (PDK1) on Thr346 to inactivate the pyruvate dehydrogenase

228 Inhibition of PDK1 or knockout of hypoxia-inducible factor 1alpha (HIF

229 Maintenance of PDK1 or LDHA expression in certain regions of the brain

230 Here, we show that overexpression of either PDK1 or LDHA in a rat CNS cell line (B12) confers resist

231 In contrast, cells expressing either PDK1 or LDHA maintained a lower mitochondrial membrane p

232 ingolipid synthesis by Myriocin, or reducing Pdk1 or Mef2 levels, all effectively suppress neurodegen

233 affected by inhibition of PI3K, knockdown of PDK1 or mTORC2 complex.

234 Targeting either PDK1 or SGK1 prevents mTORC1 activation, restoring the a

235 phosphoinositide-dependent protein kinase 1 (PDK1) or the pharmacological inhibition of its downstrea

236 The PI3K-PDK1 pathway also mediates YAP nuclear translocation dow

237 (PI3K)/phosphoinositide-dependent kinase 1 (PDK1) pathway.

238 r PDK1, also correlated with fluctuations of PDK1/PCNA in the LAN group.

239 PI3 kinase and is rescued by the removal of PDK1 (PDPK1), but does not depend on the downstream kina

240 by phosphatidylinositol-dependent kinase 1 (PDK1) phosphorylating T(308) before S(473) autophosphory

241 lycopersicum) and P. patens at the predicted PDK1 phosphorylation site, indicating that the PpPDK1 su

242 atic insulin signaling pathway, from IRS2 to PDK1 phosphorylation, were constitutively impaired in FL

243 growth, suggesting that focused blockade of PDK1/PI3K signaling might offer a new therapeutic modali

244 (2)-dependent PtdIns5P did not require mTOR, PDK1, PKB, ERK, and p38 signaling or PIKfyve, a lipid ki

245 rains in mice suggests that the cryptococcal PDK1, PKC, and likely the TOR pathways play an important

246 on PDK1 than on mTORC2, which indicates that PDK1 plays a dominant role in the Akt-mediated regulatio

247 This work demonstrates that the PDK1/PLCgamma1 complex is a potential therapeutic target

248 gy domain of PDK1 and impairs formation of a PDK1/PLCgamma1 complex.

249 ntakisphosphate (2-O-Bn-InsP5), could affect PDK1/PLCgamma1 interaction and impair PLCgamma1-dependen

250 S-GRP78 acts as an upstream regulator of the PDK1/PLK1 signaling axis to modulate c-MYC transcription

251 ia-related long non-coding RNAs (lncRNAs) in PDK1-positive tissue, we find that lncRNA H19 is respons

252 We demonstrate that PDK1 positively modulates MRCKalpha activity and drives

253 unlike PDK1 from other plants, the P. patens PDK1 protein does not bind phospholipids due to a lack o

254 inical samples revealed that both PIK3CA and PDK1 protein levels correlated with tumor progression, h

255 y increased pyruvate dehydrogenase kinase 1 (PDK1) protein levels and a decreased pyruvate dehydrogen

256 Sequence analysis of several PDK1 proteins suggests that lipid regulation of PDK1 may

257 PDK1, pT555-aPKC, and pAkt were dependent on dynamin act

258 This phenotype was reversible on PDK1 reexpression.

259 Many of the kinases activated by PDK1 regulate cellular process such as cell survival, di

260 transformation requires the activity of the PDK1-regulated AGC family of protein kinases.

261 While many of these PDK1-regulated processes are conserved across kingdoms,

262 ro and tumor growth in vivo, indicating that PDK1 regulates breast cancer growth in a manner correlat

263 that 3-phosphoinositide-dependent kinase 1 (PDK1) regulates epithelial directional migration and inv

264 cer stem cells (BCSCs), whereas depletion of PDK1 remarkably diminishes ALDH(+) subpopulations, decre

265 Akt (RxRxxSF) and PDK1 (RFxFPxFS) binding motifs are present in hBVR.

266 gene expression through an AKT-independent, PDK1-RSK2-ATF4 signalling axis.

267 means of activating Akt via p-Akt Thr-450, p-PDK1 Ser-241, or p-IRS1 Ser-636/639.

268 Then PDK1[Ser(P)(241)] phosphorylates SGK1[Ser(P)(422)] at Th

269 Here we show that activation of the PDK1/SGK1 signaling pathway with C4-ceramide (C4-CER), a

270 candidate drugs for CF directed against the PDK1/SGK1 signaling pathway, such as C4-CER, provide a n

271 Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic ma

272 r, our results highlight a role for the PI3K-PDK1 signaling pathway in mediating acquired resistance

273 Deletion of PDK1, SIN1 or YPK1 but not MPK1 affected cell viability

274 ations (>80% inhibition of Akt signaling) or PDK1 siRNA antagonized the topoisomerase poisons by dimi

275 he large majority of endosperm PPDK, whereas pdk1 specifies the abundant mesophyll form.

276 The PDK1 substrate SGK3 was determined to be an important me

277 Notably, HSC function was more dependent on PDK1 than on mTORC2, which indicates that PDK1 plays a d

278 c peptide-binding site on the protein kinase PDK1 (the PIF pocket).

279 ction phase of lamellipodia is controlled by PDK1 through an MRCKalpha-dependent mechanism.

280 and C4-CER coincidently bind PDK1 and permit PDK1 to autophosphorylate at Ser(241).

281 to this binding site, which recruits them to PDK1 to become activated.

282 e 1 (PDK1), and Dex induced translocation of PDK1 to endosomes.

283 his signaling pathway can act independent of PDK1 to support B cell growth.

284 on of 3-phosphoinositide dependent kinase 1 (PDK1) to activate SGK3.

285 phosphoinositide-dependent protein kinase-1 (PDK1) to induce phosphorylation of PLK1, which in turn i

286 This study shows the importance of PDK1, TOR and PKC signalling pathways to the basal toler

287 condition, HIF-1alpha-mediated induction of Pdk1 was found to regulate glucose oxidation by preventi

288 he PI3K pathway was marginal suggesting that PDK1 was not a rate limiting factor.

289 cket of phosphoinositide-dependent kinase-1 (PDK1) was proposed as a novel target site for allosteric

290 other PH domains, including those of ILK and PDK1, were an order-of-magnitude lower.

291 mice showed decreased expression of LDHA and PDK1 when compared with controls.

292 s ideal for functional studies of genes like PDK1 where constitutive mouse models lead to strong deve

293 ne encoding pyruvate dehydrogenase kinase 1 (PDK1), which inhibits pyruvate dehydrogenase (PDH) via p

294 , the 3-phosphoinositide-dependent kinase 1 (PDK1), which phosphorylates the activation loop of PRK2.

295 ated by phosphoinositide-dependent kinase-1 (PDK1), which was hyperstimulated in the absence of PTPN1

296 Deletion of Pdk1, which encodes a positive downstream regulator of t

297 The protein kinase PDK1, which lies at the center of the growth-factor sign

298 arch that yielded compound 4, which binds to PDK1 with 8 muM affinity.

299 Pharmacologic inhibition of PDK1 with GSK2334470 in combination with ribociclib or p

300 ion for further analysis of the evolution of PDK1 within plants.