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 activation was required for PMA-induced COX-2 transc

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

4 RSK phosphorylates the beta subunit of CCT in response t

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

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

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

8 RSKs are therefore a promising drug target for antimetas

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

10 cer, whereas inhibiting RSK activity using a RSK-specific inhibitor, 3Ac-SL0101, decreased PSA expres

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

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

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

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

15 ses in breast cancer patients with activated RSK.

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

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

18 efine the mechanism by which ORF45 activates RSKs.

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

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 ivation leads to ERK and RSK2 activation and RSK-dependent phosphorylation of transfected Shank3.

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 ppropriate levels of KSR1 coordinate ERK and RSK activation with C/EBPbeta synthesis leading to the p

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

31 ORF45 activates the cellular kinases ERK and RSK.

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

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

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

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

36 hesion molecules by 2 pathways; both IKK and RSK lead to phosphorylation of the p65 subunit of NF-kap

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 strate that METTL1 is inactivated by PKB and RSK in cells, and the potential implications of this fin

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

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

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

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

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

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

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

51 As both RSK and rpS6 are known to be important for cell prolifer

52 Bound RSK phosphorylates Ser(676) and potentiates NFATc4 DNA b

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

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

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

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

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

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

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

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

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

62 Different RSK isoforms display distinct specificities in their int

63 Thus, two amino acids that distinguish RSK from other protein kinases are sufficient to confer

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

98 phorylation receives aberrant input from ERK/RSK.

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

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

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

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

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

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

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

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

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

108 Thus, integration of the ERK/RSK signaling pathway provides a mechanism to modulate N

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

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

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

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

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

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

115 SL0101 shows remarkable specificity for RSK.

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

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

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

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

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

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

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

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

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

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

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

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

128 Increasing RSK isoform 2 (RSK2) levels in the human prostate cancer

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

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

131 Salicylate inhibited RSK in vivo and blocked the activity of RSK2 purified fr

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

133 rker for prostate cancer, whereas inhibiting RSK activity using a RSK-specific inhibitor, 3Ac-SL0101,

134 cell line MCF-10A, although SL0101 inhibits RSK in these cells.

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

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

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

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

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

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

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

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

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

144 e identification of p90 ribosomal S6 kinase (RSK) as a target of salicylate.

145 PKB and ribosomal S6 kinase (RSK) both phosphorylated METTL1 at Ser27 in vitro.

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

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

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

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

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

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

152 protein kinase p90-kDa ribosomal S6 kinase (RSK) is an important downstream effector of MAPK but its

153 p90 ribosomal S6 kinase (RSK) is an important downstream effector of mitogen-acti

154 We demonstrate that p90 ribosomal S6 kinase (RSK) is recruited to the NFAT-DNA transcription complex

155 ugh the Raf/MEK/ERK/p90 ribosomal S6 kinase (RSK) kinase cascade and show how it determines adipogeni

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

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

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

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

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

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

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

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

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

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

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

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

168 red the activity of p90 ribosomal S6 kinase (RSK).

169 ive site of p90 ribosomal protein S6 kinase (RSK).

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

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

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

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

174 a novel target of p90 ribosomal S6 kinases (RSK) 1 and 2, downstream effectors of ERK1/2.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

190 ave now identified the first small-molecule, RSK-specific inhibitor, which we isolated from the tropi

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

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

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

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

195 n of DEF-domain-containing effectors but not RSK (90 kDa ribosomal S6 kinase), which contains a D dom

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

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

198 uence in the amino-terminal kinase domain of RSK.

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

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

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

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

203 w tool to dissect the molecular functions of RSK in cancer cells.

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

205 Pharmacological inhibition of RSK dramatically suppresses epithelial cell migration in

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

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

208 y PD 184352 or pharmacological inhibition of RSK.

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

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

211 RNA interference of RSK expression confirmed that RSK regulates MCF-7 prolif

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

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

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

215 ved xenograft models with elevated levels of RSK activity.

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

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

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

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

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

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

222 not block Ang II-induced phosphorylation of RSK, whereas inhibiting mitogen-activated protein kinase

223 issue samples, suggesting that regulation of RSK has been compromised.

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

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

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

227 45, we screened known cellular substrates of RSK.

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

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

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

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

232 f some prostate cancer cells is dependent on RSK activity and support the hypothesis that RSK may be

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

254 in, which interacts with D domains, prevents RSK activation but not DEF-domain signaling.

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

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

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

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

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

260 6 kinase 2 (RSK2), a member of the p90(RSK) (RSK) family of proteins, is a widely expressed serine/th

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

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

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

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

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

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

267 nteracts with NFAT at a distinct region than RSK.

268 nterference of RSK expression confirmed that RSK regulates MCF-7 proliferation.

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

270 RSK activity and support the hypothesis that RSK may be an important chemotherapeutic target for pros

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

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

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

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

275 We show that RSK is overexpressed in approximately 50% of human breas

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

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

278 Our results suggest that RSK-mediated phosphorylation of DAPK is a unique mechani

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 Inhibiting both the RSK and IKK pathways completely blocks the Ang II-induce

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

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

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

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

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

287 is through its role in the regulation of the RSK-rpS6 signaling module.

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