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 tion of phosphoinositide-dependent kinase 1 (PDK1).

4 phosphoinositide-dependent protein kinase 1 (PDK1).

5 uggesting a regulatory loop between CDK2 and PDK1.

6 he activity of the cell survival pathway via PDK1.

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

8 375 and is associated with reduced levels of Pdk1.

9 s of Mir375 target messenger RNAs, including Pdk1.

10 ith the peptide docking motif for binding to PDK1.

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

12 ral compounds displayed high selectivity for PDK1.

13 sphorylated and its phosphorylation required Pdk1.

14 characteristics by suppressing both H19 and PDK1.

15 at the PIF-pocket, on a model protein kinase PDK1.

16 S473 and T308 phosphorylation by mTORC2 and PDK1.

17 ls vulnerable to inhibitors of AXL, p110, or PDK1.

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

19 e of the pyruvate dehydrogenase kinases 1-4 (PDK1-4) decreases the flux of carbohydrates into the TCA

20 PDK1 ablation enhanced cell cycle entry and apoptosis of

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

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

23 osphorylation and activation by its upstream PDK1 activator.

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

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

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

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

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

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

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

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

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

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

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

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

36 PDK1 also was essential for the survival and activation

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

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

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

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

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

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

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

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

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

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

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

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

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

50 pdk1 and pdk2 were inactivated individually by transposo

51 mes in major metabolic tissues revealed that PDK1 and PDK2 were ubiquitously expressed, whereas PDK3

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

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

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

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

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

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

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

59 orylation and phosphorylation events between PDK1 and SGK1.

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

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

62 atio-temporal and conformational dynamics of PDK1 and the activation of its downstream substrates.

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

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

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

66 of phosphoinositide-dependent protein kinase PDK1 and the phosphatase PTEN.

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

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

69 3-phosphoinositide-dependent protein kinase (PDK1) and enhanced transforming growth factor beta (TGFb

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

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

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

73 321 acetylation inhibits PDHA1 by recruiting PDK1, and K202 acetylation inhibits PDP1 by dissociating

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

75 r-induced uptake of bacteria, which required PDK1, and of mitogen-activated protein kinase (MAPK)- an

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

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

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

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

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

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

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

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

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

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

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

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

88 PDK1 associates with the core Hippo pathway-kinase compl

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

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

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

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

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

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

95 Pdk1-/- BM-MKs developed increased ploidy and exhibited

96 Strikingly, Pdk1-/- BM-MKs displayed a pronounced defect in DMS pola

97 Cultured Pdk1-/- BM-MKs showed impaired spreading on collagen, as

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 that appears to regulate autoinhibition and PDK1-catalyzed phosphorylation of Thr308 in the activati

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

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

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 r anionic phospholipids in the regulation of PDK1 conformational dynamics and its downstream activati

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

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

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

114 Pdk1 deficiency further dramatically increased the numbe

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 Pdk1-deficient mice (Pdk1-/-) developed a significant ma

121 y results from increased cofilin activity in Pdk1-deficient MKs.

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

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

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

125 ificantly reduced or completely prevented by Pdk1 deletion.

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

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

128 ated T cell trafficking into lymph nodes and PDK1-dependent soluble Ag uptake, costimulatory molecule

129 Pdk1-deficient mice (Pdk1-/-) developed a significant macrothrombocytopenia a

130 site and its previously unrewarding role in PDK1 downregulation, suggesting a possible therapeutic s

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

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

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

134 5 or short hairpin RNA-specific depletion of PDK1, enhanced the efficacy of reovirus-induced oncolysi

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

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

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

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

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

140 PDK1 expression suffices for its activity, owing to auto

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

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

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

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

145 rtension and RV failure, RVfib had increased PDK1 expression.

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

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

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

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

150 strand lysine of protein kinases (Lys111 of PDK1) functions as an integrator node to coordinate allo

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

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

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

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

155 I3K pathway perturbs equilibrium between the PDK1 homodimer conformations.

156 anionic phospholipids, regulating activated PDK1 homodimers.

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

158 emonstrate that phosphatidylserine maintains PDK1 in an inactive conformation.

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

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

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

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

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

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

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

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

167 resent observations reveal a pivotal role of PDK1 in the regulation of MK cytoskeletal dynamics and p

168 The present study explored the role of PDK1 in the regulation of MK maturation and polarization

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

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

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

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

173 predict the pharmacological consequences of PDK1 inhibition.

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

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

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

177 acquisition of conditioning is blocked by a PDK1 inhibitor.

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

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

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

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

182 enhance the anticancer activity of existing PDK1 inhibitors.

183 PDK1 inhibits Hippo signaling, leading to enhanced nucle

184 PDK1 inhibits pyruvate flux to mitochondrial respiration

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

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

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

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

189 ificantly less proplatelets, indicating that PDK1 is critically required for proplatelet formation.

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

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

192 PDK1 is responsible for regulating the activity of relat

193 Measurement of kinase activity showed that PDK1 is the principal isozyme regulating hepatic PDC.

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

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

196 3'-Phosphoinositide-dependent-Kinase-1 (PDK1) is a master regulator whereby its PI3-kinase-depen

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

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

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

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

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

202 Phosphoinositide-dependent protein kinase-1 (PDK1) is required for Ca2+-dependent platelet activation

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

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

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

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

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

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

209 8 and Ser-473 to extents similar to those of PDK1 knockdown or PI3K inhibition.

210 Furthermore, PDK1 knockdown reduced the expression of CDK2 suggesting

211 In human MKs, genetic PDK1 knockdown resulted in increased maturity but reduce

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

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

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

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

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

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

218 the constitutively active dimer conformer of PDK1 may be rendered inactive by small molecules that dr

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

220 1 proteins suggests that lipid regulation of PDK1 may not commonly occur in algae and nonvascular lan

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

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

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

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

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

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

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

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

229 1 increased phosphorylation of AKT, ERK-1/2, PDK1, mTOR, PTEN, GSK-3alphabeta, and p70S6K.

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

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

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

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

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

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

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

237 (PI3K), phosphoinositide-dependent kinase 1 (PDK1 or PDPK1), and protein kinase B (Akt or PKB) in the

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

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

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

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

242 and downregulation of key glycolytic genes (Pdk1, Pdk4, Ppara), also denote disturbed cardiac metabo

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

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

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

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

247 ivation of Rev-ErbA-alpha and induced a PI3K/PDK1/PKA-dependent signaling cascade.

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

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

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

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

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

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

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

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

256 We demonstrate that PDK1 positively modulates MRCKalpha activity and drives

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

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

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

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

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

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

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

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

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

266 new anionic-phospholipid-dependent model for PDK1 regulation, depicting the conformational dynamics o

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

268 Binding of two ligands to PDK1 reveal multiple hotspots of synergistic allostery w

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

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

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

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

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

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

275 activates p110 activity and AKT-independent PDK1/SGK3 signaling to promote tumorigenic phenotypes, w

276 Mitochondrial Akt-PDK1 signaling correlates with unfavorable prognostic ma

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.