ライフサイエンスコーパス: ERK5

1 could be impaired by knockdown of p130CAS or ERK5.

2 -a phenomenon fully reversible by activating ERK5.

3 dent on the mitogen-activated protein kinase ERK5.

4 -7 signaling leads to the phosphorylation of ERK5.

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

6 oire of physiological substrates of mTOR and ERK5.

7 (p38alpha, p38beta, p38gamma, p38delta) and ERK5.

8 docking site required for MEK5 activation of ERK5.

9 the PDE3A/ICER feedback loop via activating ERK5.

10 a mechanism that promotes activation of MAPK ERK5.

11 MEK5, which activates the related MAP kinase ERK5.

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

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

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

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 Stimulation of ERK5 activated nuclear factor kappaB (NFkappaB) through

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

19 reventing the feedback loop of PDE3A/ICER by ERK5 activation could inhibit progression of myocyte apo

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

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

22 To determine the physiological relevance of ERK5 activation in regulating PDE3A/ICER feedback loop,

23 ERK5 activation restores redox balance, but fails to rep

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

25 , whereas the related kinase MEKK2 regulates ERK5 activation.

26 binds MEK5, and MEKK2 activation results in ERK5 activation.

27 eration at a higher dose required to inhibit ERK5 activation.

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

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

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

31 ERK5 activity correlates with the levels of Nur77 family

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

33 le of extracellular signal-regulated kinase (ERK5, an MAPK and specific substrate for MEK5) in prosta

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

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

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

37 EK5 and MKK7, for the coordinated control of ERK5 and c-Jun N-terminal kinase activation.

38 12) families, regulate ERK1/2, JNK, p38MAPK, ERK5 and ERK6 modules by different mechanisms.

39 ERK3, ERK5 and ERK7 are other MAPKs that have distinct regulat

40 receptors and upstream of Rac, p38 MAPK, and ERK5 and establish the ErbB-Brk-Rac-p38 MAPK pathway as

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

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

43 Erk5 and p38 MAPK signaling stimulate MEF2A expression b

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

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

46 tes extracellular signal-regulated kinase 5 (ERK5) and inhibits PDE3A/ICER feedback loop.

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

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

49 timulated phosphatidylinositol 3-kinase/Akt, Erk5, and Stat3 pathways in cardiomyocytes.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

66 Knockdown of ERK5 by retroviral infection of shRNA attenuates prolact

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

84 Increased ERK5 cytoplasmic signals correlated closely with Gleason

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

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

87 ERK5-deficient cells expressing v-Src exhibited increase

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

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

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

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

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

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

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

95 This C-terminal extension encodes an ERK5 docking site required for MEK5 activation of ERK5.

96 and that the SUMOylation defective mutant of ERK5, dominant negative form of Ubc9 (DN-Ubc9), and smal

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

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

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

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

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

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

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

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

105 Analysis of ERK5 expression in matched tumor pairs (before and after

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

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

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

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

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

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

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

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

114 , and extracellular signal-related kinase 5 (ERK5) form a ternary complex through interactions involv

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

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

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

118 ERK5 functions as a platelet activator in ischemic condi

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

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

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

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

123 d MAP kinase pathways, ERK1/2, JNK, p38, and ERK5, have been implicated in different aspects of cardi

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

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

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

127 ERK5 immunoreactivity was significantly upregulated in h

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

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

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

131 esults establish the potential importance of ERK5 in aggressive prostate cancer.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

151 ERK5 induces the Nur77 orphan steroid receptor family me

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

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

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

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

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

157 Point-mutation analyses showed that ERK5 is covalently modified by SUMO at 2 conserved sites

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

159 ERK5 is known to inhibit cardiac apoptosis after myocard

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

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

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

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

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

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

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

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

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

169 A subgroup of patients showed strong nuclear ERK5 localization, which correlated with poor disease-sp

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

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

172 ERK5 MAP kinase is highly expressed in the developing ne

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

174 ith the requirement of JNK, p38 and possibly ERK5 MAP kinases in thymocyte apoptosis.

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

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

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

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

179 Platelet ERK5 may be a target for acute therapeutic intervention

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

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

182 E3A downregulation and ICER upregulation via ERK5/MEF2 activation, and also inhibited isoproterenol-i

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 -mediated reduction of shear stress-mediated ERK5/myocyte enhancer factor 2 transcriptional activity,

199 ion of ERK5, providing a direct link between ERK5, NFkappaB, and regulation of G2-M progression.

200 We conclude that a novel ERK5-NFkappaB signaling pathway plays a key role in regu

201 re and after hormone relapse, n=26) revealed ERK5 nuclear expression was significantly associated wit

202 nstructs in PC3 cells results in predominant ERK5 nuclear localization, similar to that observed in a

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

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

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

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

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

208 observed in aggressive clinical disease; (2) ERK5-overexpressing PC3 cells have enhanced proliferativ

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

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

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

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

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

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

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

216 To define the contribution of the MEK5-ERK5 pathway in T-cell development, we retrovirally expr

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

218 ustrate the critical involvement of the MEK5-ERK5 pathway in thymocyte development distinct from that

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

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

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

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

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

224 form of MEK5 to inhibit or activate the MEK5-ERK5 pathway.

225 genitors to become neurons by activating the ERK5 pathway.

226 esults in supraphysiological activity of the ERK5 pathway.

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

228 We demonstrate that Erk5 phosphorylation allows activation of PPARgamma tran

229 Finally, we found that ERK5 phosphorylation status was not significantly affect

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

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

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

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

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

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

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

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

238 Similarly, ERK5 protein expression was increased in an androgen-ind

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

240 itosis induced by constitutive activation of ERK5, providing a direct link between ERK5, NFkappaB, an

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

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

243 Erk5 regulation of peroxisome proliferator-activated rec

244 The kinase ERK5 requires p38 kinase activity and inhibits apoptosis

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

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

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

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

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

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

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

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

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

254 st a previously uncharacterized function for ERK5 signaling during brain development and raise the in

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

256 transcription factor target of p38 MAPK and ERK5 signaling is also sensitive to altered Brk expressi

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

258 2 and CD44v5 expression and instead required ERK5 signaling to Sam68.

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

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

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

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

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

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

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

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

267 1 (E3 ligase), suggesting the involvement of ERK5 SUMOylation on its transcriptional activity.

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

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

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

271 ial nitric oxide synthase expression through ERK5 SUMOylation.

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

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

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

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

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

277 2 well-known mediators of diabetes, induced ERK5-SUMOylation, and the K6R/K22R mutant, dominant nega

278 ERK5-SUMOylation, the exacerbation of LV dysfunction, an

279 jugase) or PIAS1 (E3 ligase), but not in the ERK5-SUMOylation-site defective mutant (K6R/K22R).

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

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

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

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

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

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

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

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

288 NA-PIAS1 reversed H2O2-mediated reduction of ERK5 transcriptional activity in cardiomyocytes, indicat

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

290 ERK5 transcriptional activity, but not kinase activity,

291 e data clearly defined SUMOylation-dependent ERK5 transcriptional repression independent of kinase ac

292 cating the presence of SUMOylation-dependent ERK5 transcriptional repression.

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

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

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

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

297 ERK5 wild-type transcriptional activity was inhibited by

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.