ライフサイエンスコーパス: rsk

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

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

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

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

5 S6 kinase (S6K) and p90Ribosomal S6 kinase (RSK).

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

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

8 ses in breast cancer patients with activated RSK.

9 everse inhibition of the response to DSBs by Rsk.

10 45, we screened known cellular substrates of RSK.

11 phorylation receives aberrant input from ERK/RSK.

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

13 lls was equal in cells expressing LacZ or DN-RSK.

14 ORF45 activates the cellular kinases ERK and RSK.

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

16 efine the mechanism by which ORF45 activates RSKs.

17 gnificantly inhibited in cells expressing DN-RSK (0.16+/-0.02 pH units/min) compared with Ad.LacZ (0.

18 is was significantly reduced after I/R in DN-RSK (0.9+/-0.2%) compared with nontransgenic littermate

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

42 nificantly reduced in cells expressing Ad.DN-RSK (18.6+/-2.0%) compared with Ad.LacZ (29.3+/-5.4%).

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

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

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

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

47 cipitated with PP1beta catalytic subunit and RSK-2.

48 The p90 ribosomal S6 kinase-3 gene (p90 Rsk-3, RPS6KA2) maps in this interval.

49 ncurrent elevation of phosphorylation of p90(RSK), a known NHE1 kinase.

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

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

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

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

54 66A mutant failed to cause sustained ERK and RSK activation during lytic reactivation, resulting in d

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

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

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

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

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

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

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

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

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

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

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

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

67 ved xenograft models with elevated levels of RSK activity.

68 tate cancers and other cancers with elevated Rsk activity.

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

70 cardiomyocytes with adenovirus-expressing DN-RSK (Ad.DN-RSK) and measured NHE1 activity.

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

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

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

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

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

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

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

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

79 Importantly, activation of RSK and interaction of 14-3-3 with NHE1, necessary for a

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

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

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

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

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

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

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

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

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

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

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

91 tes with adenovirus-expressing DN-RSK (Ad.DN-RSK) and measured NHE1 activity.

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

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

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

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

96 phosphorylation of the ribosomal S6 kinase (RSK) and S6, as well as cap-dependent translation.

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

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

99 ein (CREB) kinase, pp90 ribosomal S6 kinase (RSK), and c-Fos protein levels in the caudate/putamen of

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

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

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

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

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

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

106 he activation, suggesting that PKC, ERK, and RSK are required for the activation.

107 RSKs are therefore a promising drug target for antimetas

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

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

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

111 The p90 ribosomal S6 kinases (RSKs) are direct substrates of ERK and functional mediat

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

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

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

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

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

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

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

127 The activation of RSK by ORF45 is correlated with ERK activation but does

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

129 Rsk can phosphorylate the Mre11 protein directly at S676

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

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

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

133 In Xenopus, the Mos-MEK1-MAPK-p90(Rsk) cascade utilizes spindle-assembly-checkpoint compon

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

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

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

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

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

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

140 NHE1) activity in cardiac myocytes by an ERK/RSK-dependent mechanism, most likely via RSK-mediated ph

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

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

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

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

145 specific overexpression of dominant negative RSK (DN-RSK-TG).

146 Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration in

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

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

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

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

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

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

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

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

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

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

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

158 6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed serine/th

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

160 -3, and naturally resistant isolates all use rsk for resistance.

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

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

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

164 CREB transcription factor via PKC, ERK, and RSK in a retinoid receptor-independent manner in normal

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

166 Therefore, we hypothesized that inhibiting RSK in cardiomyocytes would prevent NHE1 activation and

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 o define the signaling networks regulated by RSK in melanoma.

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

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

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

173 ionally important because inhibiting IKK and RSK in vascular smooth muscle cells blocks Ang II-induce

174 To examine the role of RSK in vivo, we generated transgenic mice with cardiac-s

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 of MNKs and other pathway enzymes (ERKs and RSKs) in these cells.

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

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

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

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

185 Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizu

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

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

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

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

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

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

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

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

196 In summary, RSK is a novel regulator of cardiac NHE1 activity by pho

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

198 own configuration of the MAPK system whereby Rsk is activated not only by Erk but also by p38 through

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

200 osphorylation of AGC kinases such as S6K and RSK is also necessary for thymocyte development.

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

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

205 Different RSK isoforms display distinct specificities in their int

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

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

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

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

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

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

212 Rsk kinases play important roles in several cellular pro

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

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

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

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

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

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

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

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

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

222 ponent of CSF, acts in part by promoting the Rsk-mediated phosphorylation of the APC inhibitor Emi2/E

223 ERK/RSK-dependent mechanism, most likely via RSK-mediated phosphorylation of the NHE1 regulatory doma

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

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

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

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

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

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

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

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

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

235 ine, without affecting activation of the ERK/RSK pathway.

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

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

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

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

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

241 The RSKs phosphorylate a range of substrates involved in tra

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

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

244 We found that p90 ribosomal S6 kinase (RSK) phosphorylated serine 703 of NHE1, stimulating 14-3

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

246 RSK phosphorylates the beta subunit of CCT in response t

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

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

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

250 We report here that Rsk phosphorylation of Emi2 promotes its interaction wit

251 Emi2 residues adjacent to the Rsk phosphorylation site were important for PP2A binding

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

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

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

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

256 The WT RSK protein is dispensable for ascospore production and

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

284 h had been pre-phosphorylated by recombinant RSK; such dephosphorylation was inhibited by the PP2A-se

285 structurally different inhibitors of the MK Rsk suppressed TLR-induced endocytosis, thus defining in

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

287 nic littermate controls to 26.0+/-4.2% in DN-RSK-TG (P<0.01).

288 increased by I/R and inhibited by 70% in DN-RSK-TG (P<0.01).

289 DN-RSK-TG hearts demonstrated normal basal cardiac function

290 onary artery occlusion for 45 minutes) in DN-RSK-TG hearts was significantly reduced at 24 hours of r

291 overexpression of dominant negative RSK (DN-RSK-TG).

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 ition, depletion of p90 ribosomal S6 kinase (RSK) via siRSK1/2 completely abolished the activation, s

298 phorbol-13-acetate (TPA), phosphorylation of RSK was increased within 5 min.

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

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