ライフサイエンスコーパス: RSK

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

2 RSK levels are higher in approximately 50% of human pros

3 RSK phosphorylates the beta subunit of CCT in response t

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

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

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

7 RSKs are therefore a promising drug target for antimetas

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

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

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

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

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

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

14 ses in breast cancer patients with activated RSK.

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

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

17 efine the mechanism by which ORF45 activates RSKs.

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

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

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

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

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

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

24 Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizu

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

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

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

28 66A mutant failed to cause sustained ERK and RSK activation during lytic reactivation, resulting in d

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

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

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

32 ORF45 activates the cellular kinases ERK and RSK.

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

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

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

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

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

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

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

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

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

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

43 cipitated with PP1beta catalytic subunit and RSK-2.

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

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

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

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

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

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

50 COX-2 transcriptional activation by blocking RSK activity and Ras signaling pathway.

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

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

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

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

55 rylation site in DAPK, which is regulated by RSK.

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

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

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

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

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

61 Different RSK isoforms display distinct specificities in their int

62 n demonstrates converse actions of different RSK isoforms.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

100 phorylation receives aberrant input from ERK/RSK.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

129 ostate tissue, which suggests that increased RSK levels may participate in the rise in PSA expression

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

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

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

133 efficacy paralleling its ability to inhibit RSK in intact cells.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

168 y mediated partially by ribosomal S6 kinase (RSK).

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

199 The formation of RSK-NFATc4-DNA transcription complex is also apparent up

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

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

202 Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration in

203 Inhibition of RSK expression or RSK activity both significantly reduce

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

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

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

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

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

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

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

211 ved xenograft models with elevated levels of RSK activity.

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

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

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

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

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

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

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

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

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

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

222 45, we screened known cellular substrates of RSK.

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

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

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

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

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

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

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

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

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

232 Phosphorylation of METTL1 by PKB or RSK inactivated METTL1 in vitro, as did mutation of Ser2

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

261 6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed serine/th

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

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

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

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

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

267 1 phosphorylation, LTF, and LTEE, suggesting RSK is required for learning-related synaptic plasticity

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

269 45 F66A mutagenesis that abolishes sustained RSK activation and RSK inhibitors significantly decrease

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

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

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

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

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

275 Thus, we show that RSK has an unexpected role in proliferation of transform

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

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

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

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

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

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

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

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

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

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

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

287 Mutation of the RSK-phosphorylation site (T266A) of C/EBPbeta abrogated

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

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

290 The RSKs phosphorylate a range of substrates involved in tra

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

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

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

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

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

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

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

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

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

300 The WT RSK protein is dispensable for ascospore production and