ライフサイエンスコーパス: rsk

1 ing directly to the p90 ribosomal S6 kinase (RSK).

2 ough its substrate, p90 ribosomal S6 kinase (RSK).

3 lator of IRS-1, the p90 ribosomal S6 kinase (RSK).

4 orylation by the 90-kDa ribosomal S6 kinase (Rsk).

5 gulated kinase 1/2, protein kinase A, or p90(RSK).

6 olished phosphorylation of both NHE1 and p90(RSK).

7 y the phosphorylation status of T359/S363 in RSK.

8 thin IRS-1 falls into the consensus motif of RSK.

9 ses in breast cancer patients with activated RSK.

10 everse inhibition of the response to DSBs by Rsk.

11 45, we screened known cellular substrates of RSK.

12 KC, but not of PI3K/PKB, mTOR/p70S6K, or ERK/RSK.

13 phorylation receives aberrant input from ERK/RSK.

14 ORF45 activates the cellular kinases ERK and RSK.

15 efine the mechanism by which ORF45 activates RSKs.

16 kinase (MEKK)1/ERK/p90 ribosomal S6 kinase (RSK)1-dependent C/EBPbeta signaling pathway in thrombin-

17 interacted with ELK-1 (DEF and DEJL motifs), RSK-1 (DEJL motif), and c-Fos (DEF motif) with K(D) valu

18 ations inhibited interactions with ELK-1 and RSK-1 by 6-fold but had no effect on interactions with c

19 eractions with ERK2 but had little effect on RSK-1 interactions.

20 tus of ERK2 did not affect interactions with RSK-1 or c-Fos but did inhibit interactions with ELK-1 a

21 RSK-1 phosphorylation at Thr(359)/Ser(363) in cellular/n

22 K and GSK-3beta) or stimulates (AKT, ERK and RSK-1) mTORC1 activity(3-9).

23 ietary restriction, in daf-16/FOXO, sir-2.1, rsks-1 (ribosomal S6 kinase), gcn-2, and aak-2 (AMPK) lo

24 mutations in genes encoding raga-1 (RagA) or rsks-1 (S6K) is fully suppressed by neuronal-specific re

25 We find that rsks-1 (which encodes the worm homolog of mammalian p70S

26 Moreover, rsks-1 acts in parallel with the glp-1 (Notch) and daf-2

27 Loss of rsks-1 and ife-1 (eIF4E) together reduces the germline p

28 , we have identified the ribosomal S6 kinase RSKS-1 as a new cell-autonomous inhibitor of axon regene

29 An essential output of RSKS-1 in axon regrowth is the metabolic sensor AMP kina

30 RSKS-1 is not required for axonal development but inhibi

31 ause germline defects similar to a subset of rsks-1 mutant phenotypes.

32 The enhanced regrowth of rsks-1 mutants is partly dependent on the DLK-1 MAPK cas

33 n biosynthesis and extend lifespan, but only rsks-1 mutations require pha-4 for adult longevity.

34 In the germ line, rsks-1 promotes cell cycle progression and inhibits larv

35 d germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely insensitive to the

36 Loss of function in rsks-1 results in more rapid growth cone formation after

37 In addition, rsks-1, but not ife-2, can suppress the larval lethality

38 between diet and germline proliferation via rsks-1, loss of rsks-1 renders the germ line largely ins

39 Mutations in the predicted CeTOR target rsks-1/S6 kinase or in ife-2/eIF4E also reduce protein b

40 he TORC1 pathway components AMPK, RAGA-1 and RSKS-1/S6 kinase.

41 his result suggests that the major effect of RSK-2 is to inhibit PP1 rather than to directly phosphor

42 sphorylation of YB-1 on Ser(102) via the ERK/RSK-2 signaling pathway is necessary for FSH-mediated ex

43 bitor PD98059, or the ribosomal S6 kinase-2 (RSK-2) inhibitor BI-D1870.

44 ation of YB-1 on Ser(102) is PKA-, ERK-, and RSK-2-dependent.

45 cipitated with PP1beta catalytic subunit and RSK-2.

46 The mechanism of RSK action depends both on the isoform and the cancer ty

47 Studies have revealed that ERK-RSK activates several transcription factors involved in

48 45 F66A mutagenesis that abolishes sustained RSK activation and RSK inhibitors significantly decrease

49 ize the biological consequence of persistent RSK activation by ORF45, we screened known cellular subs

50 EGFR transactivation pathway leading to ERK-RSK activation does not lead to CREB-Ser(133) phosphoryl

51 shes ORF45-RSK interaction and sustained ERK-RSK activation during lytic reactivation and subsequentl

52 66A mutant failed to cause sustained ERK and RSK activation during lytic reactivation, resulting in d

53 l lytic replication upon sustained ORF45-ERK-RSK activation during the KSHV lytic life cycle.

54 The importance of ERK-RSK activation for KSHV viral transcription has been sho

55 s suggest a critical role for ORF45-mediated RSK activation in KSHV lytic replication.

56 evels of Rsk in PC3 prostate cancer cells or Rsk activation in other cell types promoted 14-3-3vareps

57 the operation of the noncanonical pathway of Rsk activation in these cells.

58 As a result, Rsk activation is entirely p38 dependent.

59 n production, indicating that ORF45-mediated RSK activation plays a critical role in KSHV lytic repli

60 on and pathogenesis.IMPORTANCE ORF45-induced RSK activation plays an essential role in KSHV lytic rep

61 Until recently, Rsk activation was thought to be exclusively initiated b

62 F45-RSK associations and block ORF45-induced RSK activation without interfering with S6K1 activation.

63 reas c-Fos acts as a sensor of sustained ERK-RSK activation, ORF45-ERK-RSK signaling mediates c-Fos p

64 , and C/EBP, which lead to the transient ERK-RSK activation-dependent IE transcription.

65 iates sustained ERK-p90 ribosomal S6 kinase (RSK) activation during KSHV lytic replication and facili

66 ulated kinase (ERK)-p90 ribosomal S6 kinase (RSK) activation, which is induced by an immediate early

67 Inhibition of RSK expression or RSK activity both significantly reduced CREB1 phosphoryl

68 Although increased RSK activity has been observed in stressed myocytes, the

69 The dependence of FGFR1-transformed cells on RSK activity was further confirmed in cell lines derived

70 ved xenograft models with elevated levels of RSK activity.

71 tate cancers and other cancers with elevated Rsk activity.

72 heir ability to inhibit ribosomal s6 kinase (RSK) activity and cancer cell proliferation.

73 ering RNA inhibition of ribosomal S6 kinase (RSK) activity induced death of the FGFR1-transformed cel

74 Sk-2, Sk-3, and sensitive rsk alleles differ from each other by their unique indel

75 lude basophilic protein kinases such as AKT, RSK, AMPK and ROCK.

76 s associated with cardiac pathology activate RSK, an established NHE kinase, and several selective RS

77 Here we show that RSK and Akt, which are activated downstream of Ras/ERK a

78 K17, hnRNP K, and gene expression along with RSK and CXCR3 signaling in a keratinocyte-autonomous axi

79 s to and inhibits pyrin by hijacking PRK and RSK and directing linker phosphorylation.

80 s study we demonstrate that both recombinant RSK and endogenous RSK in Xenopus egg extracts phosphory

81 As a result, the complex-associated RSK and ERK were activated and sustained at high levels.

82 extracellular signal-regulated kinase (ERK)-RSK and ETS-like transcription factor 1 (Elk1)-CHOP (C-E

83 Moreover, combined treatment with RSK and GLI inhibitors led to an enhanced apoptosis of M

84 DR5 expression through co-activation of ERK/RSK and JNK signaling pathways and subsequent cooperativ

85 hways and their downstream effectors such as RSK and MSK1/2.

86 sult of MyD88-mediated activation of MEK/ERK/RSK and p38.

87 e a strong rationale for the combined use of RSK and PI3K pathway inhibitors to elicit favorable resp

88 erminants: nuclear transport and the Ras/ERK/RSK and PI3K/Akt signaling pathways.

89 inase activity in the canonical RAF/MAPK/ERK/RSK and PI3K/AKT/PDK/mTOR/S6K pathways are identified.

90 rtnership is regulated by the ser/thr kinase RSK and required for CXCR3-dependent tumor cell growth a

91 inding that ERK inhibition corrects elevated RSK and S6 activity.

92 Both RSK and S6K phosphorylate serine 145 of Mad1 upon serum

93 phosphorylation of p90-ribosomal S6 kinase (RSK) and a concomitant activation of ETS-like transcript

94 the ERK1/2 catalytic activity readouts, p90(RSK) and ELK1, as well as the cell type-specific changes

95 cell signaling through ribosomal S6 kinase (RSK) and enhance protein translation.

96 Recently, the authors reported ERK1/2, p90(RSK) and NHE1 phosphorylation after 2 hours.

97 gical substrate for p90 ribosomal S6 kinase (RSK) and p70 ribosomal S6 kinase (S6K).

98 Mad1 is a substrate of p90 ribosomal kinase (RSK) and p70 S6 kinase (S6K).

99 nase (S6K) or the p90 ribosomal protein S6K (RSK) and results in enhanced interaction of the protein

100 ined activation of p90 ribosomal S6 kinases (RSKs) and extracellular regulated kinase (ERK).

101 rus interacts with p90 ribosomal S6 kinases (RSKs) and strongly stimulates their kinase activities.

102 rylation of Erk1/2, p90 ribosomal S6 kinase (RSK), and p38 in a temporal order.

103 t activator of the p90 ribosomal S6 kinases (RSK), and we found that this activity is necessary but n

104 ated kinase (ERK) with RSK, such that ORF45, RSK, and ERK formed high molecular mass protein complexe

105 identified multiple substrates of the mTOR, Rsk, and Mnk kinases as targets of CGP57380.

106 ons) despite reduced phosphorylation of AKT, RSK, and S6RP.

107 PKA, PKC, CKII, p38MAPK, and RSK are predicted as the major kinases for phosphorylati

108 RSKs are therefore a promising drug target for antimetas

109 hrough MEK1/2 and ERK1/2 to the effector P90(RSK) are activated in both perinatal Pkd1 and adult Pkd2

110 The p90 ribosomal S6 kinases (RSK) are implicated in various cellular processes, inclu

111 The p90 ribosomal S6 family of kinases (RSK) are potential drug targets, due to their involvemen

112 ERK1/2 cascade module, including MEK1/2 and Rsk, are found in complexes bound to these promoters.

113 ling in lobular carcinomas, thus implicating RSK as a candidate therapeutic target in FGFR1-expressin

114 FR1 in mammary epithelial cells and identify RSK as a critical component of FGFR1 signaling in lobula

115 The role of RSK as a potential therapeutic target for indirectly sup

116 Our findings identify RSK as a therapeutic target for fragile X and suggest th

117 naling in cancer cells and to fully evaluate RSK as a therapeutic target.

118 ernative" S6 kinase p90-ribosomal S6 kinase (RSK), as evidenced by the site of elevated phosphorylati

119 s, 12 blocked activation of cellular MSK and RSK, as well as downstream phosphorylation of the critic

120 lytic replication, indicating that the ORF45-RSK association is a unique target for KSHV-related dise

121 from the RSK-binding region to disrupt ORF45-RSK associations and block ORF45-induced RSK activation

122 nd to block ERK-dependent phosphorylation of RSK, at Thr-573, in its C-terminal kinase domain.

123 manner associated with activation of the ERK/RSK axis, DR5 upregulation, and elevated nuclear accumul

124 Together, these results indicated that ORF45/RSK axis-induced eIF4B phosphorylation is involved in tr

125 te that a short ORF45-derived peptide in the RSK-binding region is sufficient for disrupting ORF45-RS

126 ell-permeable ORF45-derived peptide from the RSK-binding region to disrupt ORF45-RSK associations and

127 Insulin weakly activates RSK but strongly activates the phosphoinositide 3-kinase

128 ne of the phosphatases that dephosphorylates RSK, but not ERK1/2.

129 ently only two known selective inhibitors of RSK, but the basis for selectivity is not known.

130 that the activation of a specific isoform of RSK by ORF45 also leads to increased mRNA synthesis from

131 In addition, knock down of RSK by RNAi in Aplysia sensory neurons impairs LTF, sugg

132 ERK phosphorylates most substrates, such as RSK, by targeting them through its D-domain, this well-s

133 Rsk can phosphorylate the Mre11 protein directly at S676

134 Thus, our results indicate that MEK-RSK cascade positively regulates GLI2 stabilization and

135 Thus, our results indicate that MEK-RSK cascade positively regulates GLI2 stabilization and

136 is a physiological substrate of the MEK-ERK-RSK cascade.

137 becomes activated by the Ras-Raf-MEK-ERK-p90(RSK) cascade.

138 regulation wherein MAPK signalling promotes Rsk-catalysed Apaf-1 phosphorylation and consequent bind

139 S100B-RSK complex formation was shown to be Ca(2+)-dependent a

140 t phosphorylation substrates, we defined the RSK consensus phosphorylation motif and found significan

141 on and mitochondrial targeting, regulated by RSK, defines a role for the MEK1/2-ERK1/2 cascade in T c

142 as revealed a novel ERK/ribosomal S6 kinase (RSK)-dependent mechanism that regulates DR5 expression p

143 migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood.

144 stage of KSHV lytic replication through ERK-RSK-dependent phosphorylation and stabilization and that

145 RSK-dependent Ser-260 phosphorylation was sensitive to t

146 Thus, ERK/RSK-dependent, CHOP and Elk1-mediated mechanisms are cri

147 Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration in

148 dicating a critical role for ORF45-activated RSK during KSHV lytic replication.

149 n of ERKs and a profound dependence on their RSK effectors.

150 dependent on activation of the S6K/eIF4B or RSK/eIF4B pathway.

151 ed-HCC tumors showed elevated levels of ERK, RSK, ELK1 and DR5 along with decreased expression of Ki6

152 ey role of a novel crosstalk between WA, ERK/RSK, ELK1, and DR5 in HCC inhibition.

153 Inhibition of RSK expression or RSK activity both significantly reduce

154 ew briefly presents the similarities between RSK family members before focusing on the specific funct

155 ressed myocytes, the functions of individual RSK family members have remained poorly defined, despite

156 rminal domain that is not conserved in other RSK family members.

157 While the p90 ribosomal S6 kinase (RSK) family has been implicated in multiple tumor cell f

158 p90 ribosomal S6 kinase (RSK) family members are effectors for extracellular sign

159 The ribosomal S6 kinase (RSK) family of kinases is a group of extracellular signa

160 6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed serine/th

161 gh ligand efficiency and selectivity for MSK/RSK-family kinases.

162 -3, and naturally resistant isolates all use rsk for resistance.

163 However, our understanding of RSK function in metastasis remains incomplete and is com

164 l S6 kinase (S6KII) or its mammalian homolog RSK has not been performed in the context of neuronal pl

165 Although the RSKs have a high degree of sequence homology, their func

166 ssor, our results suggest the involvement of RSK in a vast array of unexplored biological functions w

167 butes to the sustained activation of ERK and RSK in Kaposi sarcoma-associated herpesvirus lytic repli

168 or Ser-380), we found that insulin activates RSK in L6 myocytes in the absence of AA overload.

169 imotor culture system to examine the role of RSK in long-term synaptic facilitation (LTF) and long-te

170 o define the signaling networks regulated by RSK in melanoma.

171 High endogenous levels of Rsk in PC3 prostate cancer cells or Rsk activation in ot

172 se ERK and increased abundance of the kinase RSK in the dorsal horns of the spinal cord, which are he

173 egradation, suggesting an important role for RSK in the inactivation of PDCD4 in melanoma.

174 indings establish critical roles for S6K and RSK in the induction of IFN-dependent biological effects

175 ate that both recombinant RSK and endogenous RSK in Xenopus egg extracts phosphorylate all three isof

176 existence of isoform-based specificity among RSKs in mediating particular cellular processes.

177 nase (S6K) or the p90 ribosomal protein S6K (RSK) in a cell-type-specific manner.

178 in kinase (PKA) and p90 ribosomal S6 kinase (RSK) in cardiomyocyte apoptosis.

179 ted the function of p90 ribosomal S6 kinase (RSK) in the Drosophila circadian system.

180 We demonstrated that binding of ORF45 to RSK increases the association of extracellular signal-re

181 t activation and sustained activation of ERK-RSK induce viral immediate early (IE) transcription and

182 sensitive to the MEK inhibitor UO126 and the RSK inhibitor BID-1870.

183 more, targeting RSK2 with the small molecule RSK inhibitor FMK-MEA effectively attenuated the invasiv

184 Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizu

185 In addition, single agent RSK inhibitor treatment was effective in drug-naive line

186 with these results, inhibition of RSK2 by an RSK inhibitor, fmk, did not effectively induce apoptosis

187 ion, we summarize the development of current RSK inhibitors and their limitations.

188 asis and suggests ways forward in developing RSK inhibitors as new antimetastasis drugs.

189 We found that the RSK inhibitors blocked cell proliferation and protein sy

190 stablished NHE kinase, and several selective RSK inhibitors have been described recently.

191 that abolishes sustained RSK activation and RSK inhibitors significantly decreases lytic replication

192 Current RSK inhibitors target more than one RSK isoform, and thi

193 critical region of ORF45 that is involved in RSK interaction and activation.

194 point F66A mutation in ORF45 abolishes ORF45-RSK interaction and sustained ERK-RSK activation during

195 est that a small peptide that disrupts ORF45-RSK interaction might be a promising agent for controlli

196 ng region is sufficient for disrupting ORF45-RSK interaction, consequently suppressing lytic gene exp

197 ally, the overexpression of S100B sequesters RSK into the cytosol and prevents it from acting on nucl

198 r, the precise mechanisms and the isoform of RSK involved in this process remain undefined.

199 These results show that RSK is a novel regulator of insulin signaling and glucos

200 iated by Erk1/2, but in dendritic cells (DC) Rsk is also activated by p38 mitogen-activated protein (

201 Erk1/2-activated C-terminal kinase domain of Rsk is dispensable for p38-MK2/3 activation and show tha

202 Moreover, RSK is likely to be more active in mitotic cells than in

203 1 phosphorylation, LTF, and LTEE, suggesting RSK is required for learning-related synaptic plasticity

204 Ribosomal S6 kinase (RSK) is a key downstream element of the MAPK cascade.

205 The p90 ribosomal S6 kinase (RSK) is one of these kinases, although its role is poorl

206 Current RSK inhibitors target more than one RSK isoform, and this may limit their efficacy as antica

207 Four RSK isoforms have been identified in humans on the basis

208 Indeed, changes in the expression of RSK isoforms have been reported in several malignancies,

209 ement in the current data on the function of RSK isoforms in metastasis and suggests ways forward in

210 and is complicated by the fact that the four RSK isoforms perform nonredundant, sometimes opposing fu

211 Of the three widely expressed RSK isoforms, RSK2 appears to be selectively involved in

212 n demonstrates converse actions of different RSK isoforms.

213 ed difluorophenol pyridine inhibitors of the RSK kinase family as demonstrated cellularly by the inhi

214 Rsk kinases play important roles in several cellular pro

215 ed BI-D1870, a dihydropteridine inhibitor of RSK kinases, as a promising starting point for the devel

216 we review the structure and function of the RSK kinases, their role in cancer growth and survival, a

217 sphorylation of serine 897 (S897) by AKT and RSK kinases.

218 Rather, a resistant version of RSK likely neutralizes the killer element and prevents i

219 data point to Mre11 as an important locus of Rsk-mediated checkpoint inhibition acting upstream of AT

220 The ORF45/RSK-mediated eIF4B phosphorylation was distinguishable f

221 However, despite the variance in RSK-mediated outcomes, chemical inhibition of this group

222 /EBPbeta-activating modifications, including RSK-mediated phosphorylation of a bifunctional residue i

223 Inhibition of RSK-mediated phosphorylation of Cdc25 inhibits G2/M tran

224 but had no effect on the phosphorylation of RSK, MEK1/2, ERK1/2, p38 or JNKs, indicating that eriodi

225 In cancer, RSKs modulate cell transformation, tumorigenesis, and me

226 effects, low affinity, and poor efficacy of RSK modulators limit their clinical application.

227 We show here that the ribosomal s6 kinase (Rsk), often elevated in cancers, can suppress DSB-induce

228 Inducible phosphorylation by RSK on Ser273 in the leucine zipper was required for DNA

229 point mutation abolished binding of ORF45 to RSK or ERK and, consequently, its ability to activate th

230 either the p90 ribosomal protein S6 kinase (RSK) or p70 S6 kinase (S6K1), in a cell type-specific ma

231 bolished upon intrathecal inhibition of ERK, RSK, or protein synthesis.

232 RSK (p90 ribosomal S6 kinase) is a MAPK-activated protei

233 RSKs (p90 ribosomal S6 kinases) have emerged as central

234 n experiments showing that activation of MEK-RSK paralleled higher protein level of GLI2 in several m

235 es cell survival in cooperation with the ERK-RSK pathway by targeting BimEL for degradation.

236 tes CREB-Ser(133) phosphorylation via an ERK-RSK pathway in cardiac fibroblasts, the thrombin-depende

237 al-regulated kinase/p90 ribosomal S6 kinase (RSK) pathway.

238 of rapamycin/ribosomal S6 kinase and MEK/ERK/RSK pathways because it was resistant to both rapamycin

239 nes identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells.

240 (cAMP/PKA) pathway or via the AKT, MK2, and RSK pathways.

241 esults suggest that activation of ERK1/2-p90(RSK) pathways following in vitro ischemia phosphorylates

242 Moreover, engagement of the RSK/PDCD4 pathway by the type I IFNR is required for the

243 S6 PK-phosphoinositide-dependent kinase (ERK-RSK-PDK) complex is an excellent example to demonstrate

244 The RSKs phosphorylate a range of substrates involved in tra

245 p38/MK2/3-activated Rsk phosphorylated downstream targets and is physiologic

246 Moreover, recombinant RSK phosphorylated IRS-1 C-terminal fragment on Ser-1101

247 multiple mammalian cell lines and found that RSK phosphorylates myosin phosphatase-targeting subunit

248 Specifically, we demonstrate that RSK phosphorylates Nur77 at serine 354 and this modulate

249 RSK phosphorylates the beta subunit of CCT in response t

250 Our results show that RSK phosphorylates the tumor suppressor PDCD4 (programme

251 ent colon cancer cell growth by reducing ERK-RSK phosphorylation as well as increasing colon cancer c

252 An Emi2 mutant that retained Rsk phosphorylation but lacked PP2A binding could not be

253 Mutation of the ERK-RSK phosphorylation sites of c-Fos restrains KSHV lytic

254 In human HEK293 and PC-3mm2 cell lines, RSK preferentially phosphorylates Cdc25A and Cdc25B in m

255 ignal-regulated kinase 1/2 (ERK1/2) effector RSK prevents the EGF-induced myoepithelial expansion.

256 y inhibiting the myosin phosphatase, ERK and RSK promote myosin II-mediated tension for lamella expan

257 Together, these findings indicate that RSK promotes G2/M transition in mammalian cells through

258 The WT RSK protein is dispensable for ascospore production and

259 d by certain cell-based studies of mammalian RSK protein.

260 ed kinase (ERK) and p90 ribosomal S6 kinase (RSK) proteins, we found several other copurified protein

261 characterization of the Sk resistance gene, rsk (resistant to Spore killer).

262 A activated phosphorylation of the S6 kinase RSK (ribosomal S6 kinase) in breast cancer cells.

263 activation of PKD3 potentiates MEK/ERK/RSK (RSK, ribosomal S6 kinase) signaling and significantly en

264 more, activation of PKD3 potentiates MEK/ERK/RSK (RSK, ribosomal S6 kinase) signaling and significant

265 omal S6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed ser

266 Here we show that Cot/tpl2 regulates RSK, S6 ribosomal protein, and 4E-BP phosphorylation aft

267 ty of downstream AGC kinases (including Akt, RSK, S6K, SGK, and PKC).

268 rsk seems to be a fungal-specific gene, and its deletion

269 t negative RSK1 mutant (RSK1-DN) showed that RSK selectively phosphorylates IRS-1 on Ser-1101.

270 In each killer system, rsk sequences from an Sk strain and a resistant isolate

271 n sites located in the activation segment of RSK (Ser-221 or Ser-380), we found that insulin activate

272 , elevated S100B contributes to abnormal ERK/RSK signaling and increased cell survival in malignant m

273 induce DR5 expression through activating ERK/RSK signaling and subsequent Elk1 activation and ATF4-de

274 Our results reveal that the ORF45-RSK signaling axis and KSHV lytic replication can be eff

275 iptional progression following sustained ERK-RSK signaling during the KSHV lytic life cycle.

276 potency profile to examine the importance of RSK signaling in cancer cells and to fully evaluate RSK

277 r of sustained ERK-RSK activation, ORF45-ERK-RSK signaling mediates c-Fos phosphorylation and accumul

278 ined the ERK/90-kDa ribosomal S6 kinase (p90(RSK)) signaling pathways.

279 ytochrome c, suggesting a potential role for Rsk signalling in apoptotic resistance of prostate cance

280 Mechanistically, FGF4-ERK1/2-RSK signalling inhibits EPHA2 via Ser/Thr phosphorylatio

281 CCTbeta Ser-260 was identified as the RSK site by mass spectrometry and confirmed by site-dire

282 Phosphorylation of the RSK sites in these Cdc25 isoforms increases their M-phas

283 Notably, the addition of MEK- or RSK-specific inhibitors can overcome these resistance ph

284 The significance of MEK-RSK stabilization was demonstrated in experiments showin

285 a phosphorylation sites, indicating that MEK-RSK stabilizes GLI2 by controlling targeting GSK-3beta-m

286 f 14-3-3 binding proteins are also potential RSK substrates.

287 acellular signal-regulated kinase (ERK) with RSK, such that ORF45, RSK, and ERK formed high molecular

288 h step in ATM activation, we have found that Rsk targets loading of MRN complex components onto DNA a

289 system with primary kidney fibroblasts from RSK-Tg and RSK-wt mice and found that RSK-Tg fibroblasts

290 s from RSK-Tg and RSK-wt mice and found that RSK-Tg fibroblasts consistently produce excessive H(2)O(

291 ated FSP-1-specific p90RSK transgenic mouse (RSK-Tg) and discovered that these mice, after obstructiv

292 esponsible for binding and activation of ERK/RSK to a single residue, F66.

293 Activated RSK translocated from the cytoplasm to the nucleus, wher

294 hese cells LKB1 is phosphorylated by ERK and Rsk, two kinases downstream of B-RAF, and that this phos

295 haracterize the functions of ORF45-activated RSK upon KSHV lytic reactivation.

296 Inhibition of RSK using either the pharmacological inhibitor BI-D1870

297 his site or when a kinase-inactive mutant of RSK was used.

298 ained activation of p90 ribosomal S6 kinase (RSK), which is crucial for KSHV lytic replication, but t

299 h primary kidney fibroblasts from RSK-Tg and RSK-wt mice and found that RSK-Tg fibroblasts consistent

300 l damage compared with their wt littermates (RSK-wt), indicating a role of p90RSK in fibroblast-epith