ライフサイエンスコーパス: ERK5

1 canonical receptor CXCR4 and the MAP kinase ERK5.

2 ferating macrophages in human tumors express ERK5.

3 MEK5, which activates the related MAP kinase ERK5.

4 suggesting kinase-independent functions for ERK5.

5 could be impaired by knockdown of p130CAS or ERK5.

6 -a phenomenon fully reversible by activating ERK5.

7 dent on the mitogen-activated protein kinase ERK5.

8 -7 signaling leads to the phosphorylation of ERK5.

9 but not by the inhibition of ERK1/2 or BMK1/ERK5.

10 ped kinase-active, drug-resistant mutants of ERK5.

11 3 does not covalently modify p38MAPK, JNK or ERK5.

12 a mechanism that promotes activation of MAPK ERK5.

13 tes extracellular signal-regulated kinase 5 (ERK5), a MAP kinase that is specifically expressed in th

14 hat extracellular signal-regulated kinase 5 (ERK5), a member of the mitogen-activated protein kinase

15 APK extracellular signal-regulated kinase 5 (ERK5), a protein kinase known to be exquisitely sensitiv

16 Finally, we show that human ERK5, a functional ortholog of Mpk1, is similarly capabl

17 P not only stimulated prosurvival ERK1/2 and ERK5 activation but also abrogated SAPK/JNK and p38 MAPK

18 Here, we demonstrated increased ERK5 activation in 30 of 39 (76.9%) clinical tumor sampl

19 w that PKCzeta is essential for Gq-dependent ERK5 activation in cardiomyocytes and cardiac fibroblast

20 Inhibition of IGF1R with linsitinib blocked Erk5 activation in SCH-resistant cells and decreased the

21 ERK5 activation restores redox balance, but fails to rep

22 eam signaling driven by BDNF/TrkB, including ERK5 activation, and CREB-dependent gene regulation.

23 ndependent of ERK1/2 activation but required ERK5 activation.

24 , whereas the related kinase MEKK2 regulates ERK5 activation.

25 for extracellular signal regulated kinase 5 (ERK5) activation.

26 all, our results suggest that TRAF1 mediates ERK5 activity by regulating the upstream effectors of ER

27 Activation of ERK5, an atypical mitogen activated protein kinase with

28 cells, CCM2 deletion leads to activation of ERK5 and a transcriptional program that are downstream o

29 induced by membrane-targeted PTK6, including ERK5 and AKT activation.

30 vity by regulating the upstream effectors of ERK5 and also by modulating its ubiquitination status.

31 maturation and express KLF2 independently of ERK5 and IL-7.

32 We show that Erk5 and its activating kinase MEK5 are the upstream med

33 d expression of upstream regulators of KLF2 (ERK5 and MEF2).

34 reover, neurotrophins including NT3 activate ERK5 and stimulate neuronal differentiation in aNPCs in

35 main that result in nuclear translocation of ERK5 and stimulation of gene transcription.

36 We present evidence that platelets express ERK5 and that platelet ERK5 has an adverse effect on pla

37 ust be considered when assessing the role of ERK5 and the effectiveness of anti-ERK5 therapeutics.

38 Furthermore, PKCzeta phosphorylates ERK5, and mutation analysis showed that the preferred si

39 Finally, we found that p38-MAPK, JNK, ERK5, and NF-kappaB promote the attachment of human neut

40 When activated, p90RSK associated with ERK5, and this association inhibited ERK5 transcriptiona

41 own to affect MEK5, an upstream activator of ERK5, another class of MAPK with homology to ERK1/2.

42 , which differentially activate JNK, p38 and ERK5, are necessary for xenograft tumor growth and metas

43 This study newly identifies ERK5 as a key regulator of TLR2 signaling in EC and mono

44 Collectively, our findings identified ERK5 as a mediator of cancer-associated inflammation in

45 These results identify ERK5 as a novel and critical signaling mechanism underly

46 Together, our results implicate ERK5 as a novel signaling molecule regulating adult neur

47 as an enhancer of RAS activation in DIPG and ERK5 as a novel, immediately actionable molecular target

48 lts offer a preclinical proof of concept for ERK5 as a target to enhance T-cell infiltrates in prosta

49 ction, suggesting the maintenance of cardiac ERK5 as a therapeutic approach for cardiomyopathy preven

50 nt of kinase activity, but dependent on MEK5-ERK5 association.

51 esults dissect the role of the miR-211-DUSP6-ERK5 axis in melanoma tumor growth and suggest a mechani

52 mics analyses identified a role for the MEK5-ERK5 axis in the metabolism of SCLC cells, including lip

53 ceptor and Her2/Neu activation of ERK5, with ERK5 being required for metastasis.

54 suggesting that p90RSK and CHIP competes for ERK5 binding and that p90RSK activation is critical for

55 Ectopic expression of constitutively active Erk5 blocks endothelial cell morphogenesis and causes HI

56 Pharmacologic inhibitors of ERK5 blunted platelet activation and aggregation in resp

57 A RAS pathway functional screen identified ERK5, but not ERK1/2, as a RAS pathway effector importan

58 Stimulation of ERK5 by angiotensin II is blocked upon pharmacological i

59 flow and suggest that SUMOylation of p53 and ERK5 by disturbed flow contributes to the atheroscleroti

60 Knockdown of ERK5 by retroviral infection of shRNA attenuates prolact

61 nt (aa 101-200) of CHIP and the depletion of ERK5 by siRNA inhibited CHIP Ub ligase activity, which s

62 and CHIP share a common binding site in the ERK5 C-terminal domain (aa571-807).

63 e that ablating the growth regulatory kinase Erk5 can increase T-cell infiltration in an established

64 Because the ERK5 cascade is known to be involved in cardiac hypertro

65 Ablation of ERK5 in the Erk5(-/-) cells ascertains defects in NFATc4 rephosphory

66 Both disruption of ERK5-CHIP binding with inhibitory helical linker domain

67 ICER as a novel CHIP substrate and that the ERK5-CHIP complex plays an obligatory role in inhibition

68 ulin growth factor-1 (IGF-1) was mediated by ERK5-CHIP signal module via inducible cAMP early repress

69 p90RSK activation inhibits ERK5/CHIP association and CHIP Ub ligase activity.

70 RSK or an ERK5 fragment (aa571-807) inhibits ERK5/CHIP association, suggesting that p90RSK and CHIP c

71 The regulatory mechanism governing ERK5/CHIP interaction is unknown.

72 p90RSK activation is critical for inhibiting ERK5/CHIP interaction.

73 )-mediated restoration of Erk5 expression in Erk5-CKO hearts prevents cardiomyopathy.

74 t cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contractility and mi

75 role of the p90 ribosomal S6 kinase (p90RSK)/ERK5 complex in EC dysfunction in diabetes mellitus and

76 Here, we report that the protein kinase ERK5 controls the expression of a specific subset of inf

77 we hypothesized that IL-7R signaling through ERK5 could drive the expression of KLF2.

78 Suppression of ERK5 decreased DIPG cell proliferation and induced apopt

79 However, ERK5 deficiency did not alter BAFF activation of the PI3

80 Furthermore, myeloid ERK5 deficiency negatively impacted the proliferation of

81 , which correlated with impaired survival of ERK5-deficient B cells after BAFF stimulation.

82 ERK5-deficient cells expressing v-Src exhibited increase

83 dition of the Rho-kinase inhibitor Y27632 to ERK5-deficient cells expressing v-Src led to cellular ex

84 P7 expression restored podosome formation in ERK5-deficient cells.

85 ent were found to be ERK1/2 independent, and Erk5 deletion had no obvious effect on embryonic PNS.

86 Inducible erk5 deletion in adult neural stem cells of transgenic m

87 late neuronal differentiation in aNPCs in an ERK5-dependent manner.

88 This is the first evidence of Erk5-dependent transduction of signals by endogenous ang

89 possible link between SUMOylation of p53 and ERK5 detected during endothelial apoptosis and inflammat

90 Mechanistically, ERK5 directly stabilized the proto-oncogene MYC at the p

91 Activation of ERK5 downstream of p130CAS was indispensable for this pr

92 ively, these results reveal a novel role for Erk5 during bone maturation and homeostasis in vivo.

93 Interestingly, in ERK5-EKO mice, increased leukocyte rolling and impaired

94 Inducible EC-specific ERK5 knockout (ERK5-EKO) mice showed increased leukocyte rolling and im

95 l ERK5 in atherosclerosis, we used inducible ERK5-EKO-LDLR(-/-) mice and observed increased plaque fo

96 s times compared with mice transplanted with ERK5 expressing control bone marrows.

97 enes were increased in parallel with reduced Erk5 expression in cultures generated from Erk5 (fl/fl)

98 iated virus 9 (AAV9)-mediated restoration of Erk5 expression in Erk5-CKO hearts prevents cardiomyopat

99 (mitogen-activated protein kinase kinase 5)-ERK5 (extracellular signal-regulated kinase 5) signaling

100 phenotype of spinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by 6-8 weeks of age.

101 formation parameters were increased in male Erk5 (fl/fl) mice compared to wild type (WT) littermates

102 d Erk5 expression in cultures generated from Erk5 (fl/fl) mice compared to WT mice.

103 analyses showed that 100% of male and female Erk5 (fl/fl) mice had a severely deformed curved thoraci

104 pinal protrusion in Nkx3.1:Cre;Erk5 (fl/fl) (Erk5 (fl/fl)) mice by 6-8 weeks of age.

105 While CCL19-stimulated ERK5(flox/flox) naive T cells showed increased migration

106 ling from CCR7, we examined the migration of ERK5(flox/flox)/Lck-Cre murine T cells to EDG-1 ligands.

107 n to EDG-1 ligands at 48 h, the migration of ERK5(flox/flox)/Lck-Cre T cells remained at a basal leve

108 Overexpression of either p90RSK or an ERK5 fragment (aa571-807) inhibits ERK5/CHIP association

109 In addition, ERK5 function was inhibited by either TNFalpha or the tr

110 st, extracellular signal-regulated kinase 5 (ERK5) function is required for endothelial cell homeosta

111 ERK5 functions as a platelet activator in ischemic condi

112 , we report that conditional deletion of the erk5 gene in mouse neural stem cells during development

113 ERK5 kinase inhibitors fail to recapitulate ERK5 genetic ablation phenotypes, suggesting kinase-inde

114 hat platelets express ERK5 and that platelet ERK5 has an adverse effect on platelet activation via se

115 We show that ERK5 has distinct protein-protein interaction surfaces c

116 acellular signal-regulated protein kinase 5 (ERK5) has been implicated during development and carcino

117 We found that ERK5, heretofore unrecognized as mediating TLR2 activati

118 Moreover, ERK5 icKO mice have no memory 21 d after training in the

119 The ERK5 icKO mice were also deficient in contextual fear ex

120 Mechanistically, we show that ERK5 impinges on transcription factor NFATc4.

121 We find that deletion of ERK5 in adipose depots (adipo-ERK5(-/-)) increases adipo

122 e present evidence that shRNA suppression of ERK5 in adult hippocampal neural stem/progenitor cells (

123 d SUMOylation of proteins, including p53 and ERK5 in atherosclerosis formation.

124 To examine the role of endothelial ERK5 in atherosclerosis, we used inducible ERK5-EKO-LDLR

125 this, we showed that conditional deletion of ERK5 in B cells led to a pronounced global reduction in

126 We present the crystal structure of ERK5 in complex with an MKK5 construct comprised of the

127 wever, the role and regulatory mechanisms of ERK5 in EC dysfunction and atherosclerosis are poorly un

128 Prior studies suggest a protective effect of ERK5 in endothelial and myocardial cells after ischemia.

129 t facilitates PKCzeta-mediated activation of ERK5 in epithelial cells.

130 at Gp91phox activation of calpain-1 degrades Erk5 in free fatty acid (FFA)-stressed cardiomyocytes, w

131 Accordingly, inactivation of ERK5 in keratinocytes prevents inflammation-driven tumor

132 , suggesting a critical role for endothelial ERK5 in mediating the salutary effects of fluoromethyl k

133 models and that cardiac-specific deletion of Erk5 in mice (Erk5-CKO) leads to dampened cardiac contra

134 se to oxLDL and targeted genetic deletion of ERK5 in murine platelets prevented oxLDL-induced platele

135 ive mutant blocked the activation of Akt and Erk5 in response to insulin or NGF.

136 RK1/2), Jun N-terminal kinase (JNK), p38 and ERK5 in response to receptor tyrosine kinases and GTPase

137 s study is the first to investigate MEK5 and ERK5 in SCLC, linking the activity of these two kinases

138 Ablation of ERK5 in the Erk5(-/-) cells ascertains defects in NFATc4

139 of extracellular signal-regulated kinase 5 (ERK5) in adipocyte signaling.

140 of the stimulus-dependent MAPKs, ERK1/2 and ERK5, in DRG, motor neuron, and Schwann cell development

141 sing the ERK5 kinase inhibitor, Compound 26 (ERK5-IN-1), as a paradigm, we have developed kinase-acti

142 at deletion of ERK5 in adipose depots (adipo-ERK5(-/-)) increases adiposity, in part, due to increase

143 In Src-transformed cells, ERK5 induced the expression of a Rho GTPase-activating p

144 ntification of a highly potent and selective ERK5 inhibitor BAY-885 by high-throughput screening and

145 The selectivity of previously observed ERK5 inhibitors can also be rationalized using this stru

146 These findings suggest that maintaining Erk5 integrity has therapeutic potential for treating me

147 ERK5 is a key integrator of cellular signal transduction

148 We conclude that ERK5 is a novel signaling pathway regulating development

149 dial infarction (MI), we found that platelet ERK5 is activated post-MI and that platelet-specific ERK

150 llular signal-regulated kinase 1/2 (ERK1/2), ERK5 is constitutively activated in Src-transformed fibr

151 Considering that ERK5 is expressed in almost all tumor types, our finding

152 ERK5 is known to inhibit cardiac apoptosis after myocard

153 Extracellular regulated protein kinase 5 (ERK5) is a mitogen-activated protein kinase family membe

154 Extracellular-signal regulated kinase 5 (ERK5) is activated by steady laminar flow and regulates

155 acellular signal-regulated protein kinase 5 (Erk5) is lost in the hearts of obese/diabetic animal mod

156 he dual protein kinase-transcription factor, ERK5, is an emerging drug target in cancer and inflammat

157 This shows that both the ERK5 kinase and TAD must be considered when assessing th

158 We could demonstrate that inhibition of ERK5 kinase and transcriptional activity with a small mo

159 ned the X-ray crystal structure of the human ERK5 kinase domain in complex with a highly specific ben

160 Using the ERK5 kinase inhibitor, Compound 26 (ERK5-IN-1), as a par

161 Here we show that ERK5 kinase inhibitors cause paradoxical activation of E

162 However, selective ERK5 kinase inhibitors fail to recapitulate ERK5 genetic

163 cancer and inflammation, and small-molecule ERK5 kinase inhibitors have been developed.

164 signaling network to restrain the MEKK3-MEK5-ERK5-KLF2/4 pathway.

165 We propose that up-regulation of CD59 via ERK5/KLF2 activation leads to endothelial resistance to

166 nce approach demonstrated dependence upon an ERK5/KLF2 signaling pathway.

167 ta) activation by TNFalpha would inhibit the ERK5/KLF2/eNOS pathway.

168 Inducible EC-specific ERK5 knockout (ERK5-EKO) mice showed increased leukocyte

169 et causes calpain-1-dependent degradation of ERK5 leading to mitochondrial dysfunction, suggesting th

170 These data identify a new MEK5-ERK5-lipid metabolism axis that promotes the growth of S

171 ed cardiomyocytes, whereas the prevention of Erk5 loss by blocking Gp91phox or calpain-1 rescues mito

172 ERK5 maintained the capacity of macrophages to prolifera

173 tivator in ischemic conditions, and platelet ERK5 maintains the expression of some platelet proteins

174 ERK5 MAP kinase is highly expressed in the developing ne

175 r study reveals a critical role for the MEK5-ERK5 MAP kinase signaling pathway in BAFF-induced mature

176 onserved in an interaction between the human ERK5 MAPK and human Paf1.

177 While the individual roles of TAK1, ERK5 (MAPK7) and TGF-beta pathways in endothelial cell r

178 The protein kinase ERK5 (MAPK7) is an emerging drug target for a variety of

179 causes the activation of ERK1/2, JNK1/2, and ERK5 MAPKs and AP1 and SP1, which stimulate the expressi

180 Platelet ERK5 may be a target for acute therapeutic intervention

181 ermore, our data suggest a critical role for ERK5-mediated adult neurogenesis in pattern separation,

182 vestigate whether p90RSK activation inhibits ERK5-mediated CHIP activation, and subsequently increase

183 in response to activation of a Trk-dependent ERK5/MEF2 pathway, and our data indicate that this pathw

184 induced KLF2 expression in part through the ERK5/MEF2 pathway.

185 Thus, activation of an ERK5/MEF2D transcriptional program establishes and maint

186 activated post-MI and that platelet-specific ERK5(-/-) mice have less platelet activation, reduced MI

187 ar localization of NFATc4 are found in adipo-ERK5(-/-) mice.

188 also find attenuated PKA activation in adipo-ERK5(-/-) mice.

189 ylation and impaired PKA activation in adipo-ERK5(-/-) mice.

190 red glucose handling are also found in adipo-ERK5(-/-) mice.

191 Here we report that ERK5 mitogen-activated protein kinase is specifically ex

192 ty of Mef2c/d through phosphorylation by the Erk5 mitogen-activating kinase.

193 by extracellular signal-regulated kinase 5 (ERK5) mitogen-activated protein kinase as well.

194 tudy highlights the importance of the p90RSK/ERK5 module as a critical mediator of EC dysfunction in

195 ice, the latter of which exhibited increased Erk5 mRNA expression.

196 Interestingly, ERK5 mutant mice have smaller OB and are impaired in odo

197 ricular zone and rostral migratory stream of ERK5 mutant mice.

198 arrow transplantation from platelet-specific ERK5 null mice into hyperlipidemic apolipoprotein E null

199 Aberrant vascularization in the Erk5-null mice suggested a link to angiogenesis.

200 tivity, which suggests an obligatory role of ERK5 on CHIP activation.

201 F1 expression enhances the ubiquitination of ERK5 on lysine 184, which is necessary for its kinase ac

202 n vivo, either cardiac-specific depletion of ERK5 or overexpression of p90RSK inhibits CHIP activity

203 ey, brain, and fibroblasts, but no change in ERK5, p38, or c-Jun N-terminal kinases activation.

204 , proinflammatory profile, and activation of ERK5/p38 pathways leading to vascular inflammation and r

205 uces CGN apoptosis by repressing unique MEK5/ERK5, p90Rsk, and Akt-dependent prosurvival pathways, ul

206 d inhibition of Rac suppresses distinct MEK5/ERK5, p90Rsk, and Akt-dependent signaling cascades known

207 ces compared with ERK2, which is the closest ERK5 paralog.

208 maintenance, and they also pinpoint the Bmk1/Erk5 pathway as a critical mediator of endothelial Pak2

209 KCzeta is required for the activation of the ERK5 pathway by Gq-coupled GPCR in neonatal and adult mu

210 therapeutic potential of targeting the MEK5-ERK5 pathway in breast cancer.

211 ndependent cell growth, the role of the MEK5-ERK5 pathway in the progression of clinical breast carci

212 (PKCzeta), leading to the stimulation of the ERK5 pathway independent of the canonical effector PLCbe

213 crophage (BMDM) cultures with small molecule ERK5 pathway inhibitors increased osteoclast numbers.

214 en together, our findings show that the MEK5-ERK5 pathway mediates progression to an ER(-), mesenchym

215 nical TGF-beta pathway and by activating the ERK5 pathway which restores redox signalling.

216 hese mice fail to promote the changes in the ERK5 pathway, in gene expression patterns, and in hypert

217 tion linked to stimulation of the IGF1R-MEK5-Erk5 pathway, which accounted for resistance.

218 ectly inhibiting the expression of DUSP6, an ERK5 pathway-specific phosphatase and now shown to be an

219 esults in supraphysiological activity of the ERK5 pathway.

220 of genes dysregulated by aberrant MEK1/2 or ERK5 pathways that could contribute to the NS-associated

221 he activation of NF-kappaB, JNK1/2, p38, and ERK5 pathways.

222 lipidomics analyses showed that loss of MEK5/ERK5 perturbs several lipid metabolism pathways, includi

223 We demonstrate that Erk5 phosphorylation allows activation of PPARgamma tran

224 s in this Galphaq region completely abrogate ERK5 phosphorylation, indicating that Galphaq/PKCzeta as

225 resistance was associated with an increased ERK5 phosphorylation.

226 ced extracellular signal-regulated kinase-5 (ERK5) phosphorylation and the expression of AP-1 family

227 Finally, aortic en face analysis of ERK5/PKCzeta activity showed high PKCzeta and ERK5 stain

228 stream ERK5-regulated proteins is reduced in ERK5(-/-) platelets post-MI.

229 In addition, phosphorylation of NFATc4 by ERK5 primes subsequent phosphorylation mediated by CK1al

230 We conclude that ERK5 promotes Src-induced podosome formation by inducing

231 tive MEK5, an upstream activating kinase for ERK5, promotes neurogenesis in cultured aNPCs and in the

232 oubly mutant in prostate tissue for Pten and Erk5 (prostate DKO) exhibited a markedly increased media

233 These results suggest that ERK5 provides a common bypass route in intestinal epithe

234 Furthermore, the expression of downstream ERK5-regulated proteins is reduced in ERK5(-/-) platelet

235 However the mechanisms by which endogenous Erk5 regulates angiogenesis remain unknown.

236 Erk5 regulation of peroxisome proliferator-activated rec

237 The kinase ERK5 requires p38 kinase activity and inhibits apoptosis

238 In addition, p90RSK directly phosphorylated ERK5 S496 and reduced endothelial nitric oxide synthase

239 We also identified ERK5-S496 as being directly phosphorylated by p90RSK and

240 is through binding to and phosphorylation of ERK5-S496.

241 horylated by p90RSK and demonstrated that an ERK5-S496A mutant significantly impairs Angiotensin II-m

242 Notably, depletion of MEK5/ERK5 sensitized SCLC cells to pharmacologic inhibition o

243 The dominant negative MEK5 mutant and Erk5 shRNA diminished PEDF-dependent apoptosis, inhibiti

244 These data suggest ERK5 signaling as a critical regulator of adult hippocam

245 physiological role for the Galpha(q)/PKCzeta/ERK5 signaling axis.

246 The Rac1 and ERK5 signaling cascade mediate FSP-1-induced responses i

247 membrane and suggests that the PTK6-p130CAS-ERK5 signaling cascade plays an important role in cancer

248 determine the cellular effect of disrupting ERK5 signaling from CCR7, we examined the migration of E

249 Here we find that the MEK5/ERK5 signaling pathway is associated with resistance to

250 Activation of the IGF1R-MEK5-Erk5 signaling pathway opposes pharmacologic inhibition

251 imulate proliferation of SMCs through a MEK5-ERK5 signaling pathway that can be suppressed by a domin

252 o SCH involved stimulation of the IGF1R-MEK5-Erk5 signaling pathway, which counteracted inhibition of

253 2 and CD44v5 expression and instead required ERK5 signaling to Sam68.

254 y contrast, ectopic activation of endogenous ERK5 signaling via expression of constitutive active MEK

255 increased extracellular regulated kinase 5 (ERK5) signaling, a pathway not previously known to be in

256 that abates TGF-beta signalling and enhances ERK5 signalling may be useful to counteract endothelial

257 y activation and that shear stress activates ERK5 signalling while attenuating TGF-beta signalling.

258 In addition, depletion or inhibition of ERK5 significantly increased survival of mice intracrani

259 p38s and JNKs, allow for the development of ERK5-specific inhibitors.

260 nducible and conditional knock-out (icKO) of erk5 specifically in neural progenitors of the adult mou

261 nally, inducible and conditional deletion of ERK5 specifically in the neurogenic regions of the adult

262 RK5/PKCzeta activity showed high PKCzeta and ERK5 staining in the athero-prone region.

263 q modulator, led to a complete abrogation of ERK5 stimulation.

264 1 (E3 ligase), suggesting the involvement of ERK5 SUMOylation on its transcriptional activity.

265 in endothelial cells overexpressing p53 and ERK5 SUMOylation site mutants.

266 In addition, ERK5 SUMOylation was increased in the aortas from diabet

267 e role of the disturbed flow-induced p53 and ERK5 SUMOylation, we used de-SUMOylation enzyme of sentr

268 ial nitric oxide synthase expression through ERK5 SUMOylation.

269 H(2)O(2) and AGE induced endogenous ERK5 SUMOylation.

270 To investigate the pathological role of ERK5-SUMOylation in DM mice after MI, we used cardiac sp

271 e current study, we investigated the role of ERK5-SUMOylation in ERK5 transcriptional activity as wel

272 e form of MEK5alpha (CA-MEK5alpha) inhibited ERK5-SUMOylation independent of kinase activity, but dep

273 The ERK5-SUMOylation was increased in the DM+MI, but not in

274 elopment, thereby strengthening the value of ERK5-targeted therapies to restore antitumor immunity th

275 e role of ERK5 and the effectiveness of anti-ERK5 therapeutics.

276 In addition, we found that anti-ERK5 therapy cooperates synergistically with existing an

277 eting tumor-associated inflammation via anti-ERK5 therapy may have broad implications for the treatme

278 hese findings offer a new rationale for anti-ERK5 therapy to improve cancer patient outcomes by block

279 s show that PKCzeta binds and phosphorylates ERK5, thereby decreasing eNOS protein stability and cont

280 that d-flow increases SUMOylation of p53 and ERK5 through downregulation of sentrin/SUMO-specific pro

281 d, PKCzeta was demonstrated to directly bind ERK5 thus acting as a scaffold between Galphaq and ERK5

282 ted the contribution of the MAPK module MEK5-ERK5 to SCLC growth.

283 mediators of diabetes, negatively regulated ERK5 transcriptional activity and laminar flow-induced e

284 ed with ERK5, and this association inhibited ERK5 transcriptional activity and upregulated vascular c

285 investigated the role of ERK5-SUMOylation in ERK5 transcriptional activity as well as on DM-mediated

286 These results demonstrated that ERK5 transcriptional activity is subject to downregulati

287 e inhibitors cause paradoxical activation of ERK5 transcriptional activity mediated through its uniqu

288 ith these mutants, we show that induction of ERK5 transcriptional activity requires direct binding of

289 ERK5 transcriptional activity, but not kinase activity,

290 such as hippo, Ubiquitin-proteasome system (ERK5), Tsc1/Tsc2 complex, FoxO1, wnt/beta-catenine signa

291 PKCzeta was found to bind to ERK5 under basal conditions with coimmunoprecipitation a

292 hus acting as a scaffold between Galphaq and ERK5 upon GPCR activation.

293 of extracellular signal-regulated kinase 5 (ERK5) via upregulation of myocyte enhancer factor 2 (MEF

294 SUMOylation of p53 and ERK5 was induced by disturbed flow but not by steady lam

295 ERK5 was required for optimal BAFF up-regulation of Mcl1

296 ERK5 was required for supporting the proliferation of ma

297 MEK5 and ERK5 were required for optimal survival and expansion of

298 er, these results demonstrate integration of ERK5 with NFATc4 nucleo-cytoplasmic shuttling and PKA ac

299 h factor receptor and Her2/Neu activation of ERK5, with ERK5 being required for metastasis.

300 of extracellular signal-regulated kinase 5 (ERK5) within eight hours of stimulation.