ライフサイエンスコーパス: MEK1

1 MEK1 and RSK2 failed to augment the half-life of GLI2 la

2 MEK1 has recently been shown to translocate to the nucle

3 MEK1 inhibitors blocked anti-Siglec-8/IL-5-induced cell

4 MEK1 inhibitors, which are approved to treat several for

5 MEK1 interacts with the nuclear receptor corepressor sil

6 MEK1 is recruited to the promoter of c-Fos upon TCR stim

7 MEK1 phosphorylates ERK1/2 and regulates T cell generati

8 MEK1 reduces the nuclear level of SMRT in an activation-

9 MEK1 triggers a complex pattern of early T cell activati

10 MEK1 was required to make Xenopus pluripotent cells comp

11 MEK1/2 (MAPKK1/2) inhibition promoted an epithelial phen

12 MEK1/2 and BRAF(V600E) inhibitors are used to treat BRAF

13 MEK1/2 and p38 inhibitors suppressed EP1-mediated beta1-

14 MEK1/2 and the protein phosphatase PP2A were also presen

15 MEK1/2 can be activated by numerous molecules including

16 MEK1/2 inhibitors such as AZD6244 are in clinical trials

17 MEK1/2 signaling inhibition reduced extracellular lactat

18 d mitogen-activated protein kinase kinase 1 (MEK1) and extracellular signal-regulated kinase (ERK), r

19 s reduced by inhibitors of MAP/ERK kinase 1 (MEK1) and p38 but not JNK.

20 press oncogenically activated MAPK kinase 1 (MEK1).

21 MAP-extracellular signal-regulated kinase 1 (MEK1).

22 e mitogen-activated protein kinase kinase-1 (MEK1) stimulates its kinase activity, and that acetylate

23 ; MET amplification, 5 (<1%); NRAS, 5 (<1%); MEK1, 1 (<1%); AKT1, 0.

24 1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1

25 hosphatidylinositol 3-kinase-Akt, Ras-Raf-1, MEK1/extracellular signal-regulated kinase, sphingolipid

26 rols interstack Golgi connections in a Raf-1/MEK1-dependent manner, a process required for entry of t

27 (AKTi) and selumetinib (AZD6244/ARRY-142886, MEK1/2i) or cetuximab.

28 d extracellular signal-regulated kinase 1/2 (MEK1/2) and Src inhibitors can abolish constitutively ac

29 edly inhibited by a MAPK/ERK kinase 1 and 2 (MEK1/2) inhibitor (U0126), partially blocked by a p38 in

30 ibition of p38 and MAPK/ERK kinases 1 and 2 (MEK1/2) reduced expression of BZLF1 and virus production

31 ylation of five phosphoproteins (ERK1 and 2, MEK1/2 [MAPKK], STAT3, and SAPK/JNK), and decreased leve

32 A MEK1/2-specific inhibitor was found to block CSF1-induce

33 ogical inhibition of the MEK1/2 pathway by a MEK1/2 inhibitor (MEKi) significantly increased expressi

34 In contrast, a MEK1/2 inhibitor (ERK pathway) completely abolished argi

35 Conversely, a MEK1-MEK5 chimaera that phosphorylated ERK1/2 independen

36 investigated the antileukemia activity of a MEK1 and FLT3 dual inhibitor, E6201, in AML cells resist

37 important therapeutic strategy, given that a MEK1/2 inhibitor provides a survival advantage in metast

38 immune regulatory processes through which a MEK1/2 inhibitor approach controls malaria parasitemia a

39 body demonstrates that endogenous acetylated MEK1 is extensively enriched in the nucleus following ep

40 tes its kinase activity, and that acetylated MEK1 is under the regulatory control of the sirtuin fami

41 AT2B and GIT1 require each other to activate MEK1/ERK and increase growth.

42 onse to H-RasV12, B-RAF-V600E, and activated MEK1.

43 Constitutively activated MEK1 prolonged the half-life of GLI2 and increased its n

44 as-induced nuclear accumulation of activated MEK1/2 was reliant on downregulation of the spatial regu

45 These two activating MEK1 mutations had not previously been observed in vivo

46 AG-OCT4A alone or with constitutively active MEK1 (MEK1(CA)), and we observed that the extent of OCT4

47 cells by co-expressing constitutively active MEK1 and Src rather than either alone.

48 in which expression of constitutively active MEK1 in differentiating epidermal cells results in chron

49 versely, expression of constitutively active MEK1 leads to a major increase in numbers of astrocytes

50 ed by co-expression of constitutively active MEK1 or MAPK-interacting kinase 1 (MNK1) as well as by s

51 Finally, expressing constitutively active MEK1 rescues BG formation and cerebellar foliation in Sh

52 troviral expression of constitutively active MEK1 restores tolerance upon sCD40L, but not IL-6, stimu

53 specific expression of constitutively active MEK1 was sufficient to rescue the sympathetic innervatio

54 ich could be rescued by expression of active MEK1.

55 PD198306, an orally active MEK1/2 inhibitor, acted as an uncoupler.

56 1 constitutive activity, but how they affect MEK1 regulation and function remains largely unknown.

57 onse rate (RR) for the selective, allosteric MEK1/MEK2 inhibitor trametinib (GSK1120212), in patients

58 Additionally, we observed that, although MEK1 negatively regulates TLR2 signaling in EC, MEK1 pro

59 nd suggest that co-targeting of PAK1/2/3 and MEK1/2 may be effective in the treatment of patients wit

60 Blockade of PI3K/Akt and MEK1/2 kinase pathways completely abrogated lung injury.

61 C5a caused activation of the PI3K-Akt and MEK1/2-ERK1/2 pathways, resulting in induction of IL-10,

62 ed by apoptosis responses using PERK/Akt and MEK1/ERK2 signaling, respectively.

63 The data show that antioxidants and MEK1 inhibitors reduce the cytotoxic and myotoxic effect

64 switch with the Src inhibitor (AZD0530) and MEK1/2 inhibitor (AZD6244) induced apoptosis in a large

65 Combined inhibition of BRAF and MEK1/2 (CIBM) improves therapeutic efficacy of BRAF-muta

66 New, highly selective inhibitors of BRAF and MEK1/2 have shown promise in clinical trials, including

67 ular kinases such as p38 MAPK, Src, JNK, and MEK1/2.

68 PPARalpha protein content via NF-kappaB and MEK1/2 signaling pathways and inhibits PPARalpha binding

69 Inhibitors against PI3K (LY294002) and MEK1/2 (UO126) efficiently blocked IL-33-induced prolife

70 troduction of constitutively active MEK6 and MEK1 to DU145 cells cocultured with hepatocytes abrogate

71 ppearance of secondary mutations in NRAS and MEK1 in subsets of patients.

72 ignaling pathway that is governed by p38 and MEK1/2.

73 lar kinases such as p38 MAPK, JNK, PI3K, and MEK1/2 are involved in OPN activation.

74 veral additional genes, including PIK3CA and MEK1, and receptor tyrosine kinase fusions, were also id

75 an effect that was blocked by PKA, PKB, and MEK1 inhibitors.

76 nd cytokines activate ERK1/2 by PKCdelta and MEK1/2.

77 ndothelial TJ disruption in a PKCepsilon and MEK1-ERK1/2-dependent manner.

78 ors targeting all three coactivated RTKs and MEK1 was needed to inhibit proliferation and induce apop

79 l motility (PAM), is controlled by c-Src and MEK1/2-ERK1/2.

80 Dysbindin in the activation of RhoA-SRF and MEK1-ERK1 signaling pathways and in the induction of car

81 induced cardiac hypertrophy via RhoA-SRF and MEK1-ERK1 signaling pathways.

82 Neuroprotection was dependent on VEGFR2 and MEK1/2 activation but not on p38 or phosphatidylinositol

83 s of a series of single entity, bifunctional MEK1/PI3K inhibitors achieved by covalent linking of str

84 Concurrent inhibition of both MEK1/2 and PI3K was necessary to inhibit PAR2-induced su

85 BRAF inhibitors can sequester a dormant BRAF-MEK1 complex resulting in pathway inhibition.

86 Here we show that stable BRAF-MEK1 complexes are enriched in BRAF(WT) and KRAS mutant

87 ed the frequency of secondary KRAS/NRAS/BRAF/MEK1 gene mutations in the largest collection to date of

88 ro-apoptotic BAD at Ser(112) and Ser(136) by MEK1/2 and PI3K-dependent signaling, respectively.

89 propose that after the activation of ERK1 by MEK1, subsequent slower phosphorylation of the flanking

90 homeostatic regulation of T cell function by MEK1.

91 anscription and is additionally modulated by MEK1/2, JNK, and PI3K pathways.

92 nd a Y210F mutant could not be recognized by MEK1 for phosphorylation of T202 and Y204 in vitro.

93 itch of cortical progenitors is regulated by MEK1 and MEK2.

94 unctional inhibitor strategy toward combined MEK1/PI3K inhibition.

95 Thus, concomitant MEK1 and Ventx2 knockdown restored the competence of emb

96 Concurrent MEK1 and PI3K inhibition was demonstrated with inhibitor

97 Conversely, MEK1 activation enhanced CD44 expression and promoter ac

98 that flotillin-1 forms a complex with CRAF, MEK1, ERK, and KSR1 (kinase suppressor of RAS) and that

99 MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interaction.

100 iving cells found that structurally distinct MEK1/2 inhibitors had an immediate, dose-dependent effec

101 Each MEK1/2 inhibitor depleted phosphorylated ERK1/2 and inhi

102 1 negatively regulates TLR2 signaling in EC, MEK1 promotes TLR2 signaling in monocytes.

103 uorescence revealed that EGF-activated EGFR, MEK1/2 and ERK1/2 co-localize on endosomes.

104 ating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples i

105 y mutated gene in PTNFL was MAP2K1, encoding MEK1, with a mutation frequency of 43%.

106 ously found that copper (Cu) influx enhances MEK1 phosphorylation of ERK1/2 through a Cu-MEK1 interac

107 plasma membrane is sufficient for extending MEK1/2 and ERK1/2 activities.

108 gene via NF-kappaB and, to a lesser extent, MEK1/2 signaling pathways, whereas TNFalpha-mediated sti

109 latory helix of the MAP2K1 gene encoding for MEK1.

110 treated with U0126, a specific inhibitor for MEK1/2/ERK1/2, whereas MEK2 did not affect CSFV replicat

111 kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulation of interhomolog crossover formati

112 lation event is necessary and sufficient for MEK1 activity.

113 Notably, genetic (MEK1 silencing) or chemical (U0126) inhibition of ERK si

114 Taken together, these results reveal how MEK1/2 inhibition affects cancer cell metabolism in the

115 ction of up to milligram quantities of human MEK1 kinase.

116 Specifically, we synthesize human MEK1 kinase with two serines or two phosphoserines, from

117 a(2+) and is mediated by a novel Galpha(i)-, MEK1/2-, and JNK1/2-dependent pathway.

118 Importantly, MEK1 activity was necessary to clear the pluripotency pr

119 isoforms or BMDM from targeted deficiency in MEK1 and MEK2, we show that rapamycin treatment led to a

120 ntly identified ERK1/2-inducing mutations in MEK1 and MEK2 (MEK1/2) MAPK genes in melanoma confer res

121 ths of existing and newly found mutations in MEK1 and other pathway components, providing the first s

122 of CTR1 (Cu transporter 1), or mutations in MEK1 that disrupt Cu binding, decreased BRAF(V600E)-driv

123 Baseline mutations in MEK1(P124) coexisting with BRAF(V600) were noted in seve

124 assay, we assessed 16 mutations reported in MEK1, a MAPK kinase, and provide a robust ranking of the

125 Several of these mutations result in MEK1 constitutive activity, but how they affect MEK1 reg

126 e, initiating downstream cascades, including MEK1/ERK activation and paxillin phosphorylation on S126

127 d other upstream kinase components including MEK1/2 and c-Src.

128 been found in cancers and shown to increase MEK1 activity.

129 ndothelial cell dysfunction due to increased MEK1 activity.

130 ckdown of SIRT1 or SIRT2 proteins, increases MEK1 acetylation and subsequent phosphorylation of the e

131 selective inhibition of Rac does not inhibit MEK1/2/ERK1/2 or activate JNK/c-Jun.

132 PD98059 inhibited MEK1 whereas TPCK suppressed S6K1 activity; however, the

133 e inhibitors, we demonstrate that inhibiting MEK1/2, the upstream kinases of ERK1/2 signaling, alters

134 tes minimal paradoxical activation, inhibits MEK1/2 phosphorylation, and exhibits anti-tumor activiti

135 th the clinical copper chelator TTM inhibits MEK1/2 kinase activity and reduces BRAF(V600E)-driven tu

136 In SCD mice, 0.025, 0.05, or 0.1 mg/kg MEK1/2 inhibitor also reversed leukocyte and erythrocyte

137 clinically relevant protocol, 0.3 or 1 mg/kg MEK1/2 inhibitor given to TNF-alpha-pretreated nude mice

138 Administration of 0.2, 0.3, 1, or 2 mg/kg MEK1/2 inhibitor to TNF-alpha-pretreated nude mice befor

139 an inhibitor of the ERK1/2-activating kinase MEK1, but not by inhibitors of other MAP kinases such as

140 the mitogen-activated protein kinase kinase MEK1/2, and ERK, coinciding with reductions in recruitme

141 ow that the mitogen-activated protein kinase MEK1 modulates GLI2 both at the mRNA and protein level.

142 tes mitogen-activated protein kinase kinase (MEK1/2) and extracellular signal-regulated kinase (ERK1/

143 bition and mitogen-activated protein kinase (MEK1/2) inhibition.

144 inase kinase/extracellular regulated kinase (MEK1/2/ERK1/2) cascade is involved in the replication of

145 eaks (DSBs) and the meiosis-specific kinase, MEK1/MRE4, demonstrating a role for MEK1 in the regulati

146 ets, we show that the ERK activator kinase1 (MEK1) displays increased phosphorylation in all tumors.

147 phorylation of the mitogen-activated kinases MEK1,2/ERK1,2 and increasing downstream gene expression.

148 inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib.

149 RK1 and ERK2, as well as to the MAPK kinases MEK1 and MEK2.

150 late activation of the ETS upstream kinases MEK1/2 and ERK1/2, resulting in enhanced ETS factor acti

151 experiments confirmed a reduction in MAP2KI (MEK1) expression and phosphorylated-extracellular signal

152 ated mitogen-activated protein kinase (MAPK)-MEK1/2-ERK-ELK1 and NFkappaB signaling pathways.

153 We found that MAT2B and GIT1-mediated MEK1/2 activation was not mediated by PAK1 or Src in Hep

154 Thr-770/772 residues via PKCepsilon-mediated MEK1-ERK1/2 activation, causing ZO-1 dissociation from o

155 that mortalin facilitates PP1alpha-mediated MEK1/2 dephosphorylation by promoting PP1alpha-MEK1/2 in

156 acellular signal-regulated kinase (ERK; MEK) MEK1/2 to drive neoplastic transformation.

157 4A alone or with constitutively active MEK1 (MEK1(CA)), and we observed that the extent of OCT4 ubiqu

158 ERK1/2-inducing mutations in MEK1 and MEK2 (MEK1/2) MAPK genes in melanoma confer resistance to emer

159 regulated in keratinocytes expressing mutant MEK1 and in the epithelial compartment of InvEE tumours,

160 on of which was sufficient to restore normal MEK1/2 localization and a reversal of Ras-induced prolif

161 lso promote survival of mDCs through a novel MEK1/2-ERK1/2-AMPK signaling axis.

162 h properties, suggesting that acetylation of MEK1 has oncogenic potential.

163 of the inhibitors, whereas the activation of MEK1/2 and ERK1/2 was abrogated.

164 cell EMT through simultaneous activation of MEK1/2 and Src signaling pathways.

165 3 protein secretion depends on activation of MEK1/2, p38, and JNK in HepG2 cells.

166 the apoptotic effector BAD and activation of MEK1/2.

167 Interestingly, the activities of MEK1/2 and ERK1/2 remained high beyond the point of the

168 We tested the therapeutic benefits of MEK1/2 inhibitors in reversing vasoocclusion in nude and

169 This study suggests that cocktail of MEK1/2 and Src inhibitors represents an effective therap

170 ons destabilize the inactive conformation of MEK1, resulting in its constitutive activity and making

171 ce with the TGFbeta pathway is downstream of MEK1/2 and involves phosphorylation of neither ERK1/2 no

172 isolated from the tissues and the effects of MEK1 and 2 inhibitors were assessed.

173 have identified a novel nuclear function of MEK1.

174 Phosphate induction of MEK1/2-ERK1/2 phosphorylation in hypertrophic chondrocyt

175 tors displayed potent in vitro inhibition of MEK1 (0.015 < IC50 (nM) < 56.7) and PI3K (54 < IC50 (nM)

176 extinction with pharmacologic inhibition of MEK1 in tumor spheres and in vivo.

177 1 signaling by pharmacological inhibition of MEK1 kinase in Huh7 cells caused de-repression of CYP3A4

178 Inhibition of MEK1/2 activity using PD98059 and U0126 reduced Fra-1 ex

179 rthermore, we demonstrate that inhibition of MEK1/2 with trametinib increased sensitivity of ALL cell

180 ondrial inhibition rather than inhibition of MEK1/2.

181 of cell-cycle arrest caused by inhibition of MEK1/2.

182 l migration were suppressed by inhibition of MEK1/2/ERK1/2 signaling.

183 oral PD325901, a small-molecule inhibitor of MEK1 and MEK2 (factors in the MAPK signaling pathway), a

184 may provide a highly selective inhibitor of MEK1/2 for use as a cancer therapeutic.

185 and activity of selumetinib, an inhibitor of MEK1/2, for patients with this cancer.

186 Selumetinib is an inhibitor of MEK1/MEK2, downstream of KRAS, with preclinical evidence

187 UO126, a highly selective inhibitor of MEK1/MEK2, inhibited telomerase activity and hTERT mRNA

188 T cells, we demonstrate that a low level of MEK1 is present in the nucleus of CD4 T cells under basa

189 Enforced nuclear localization of MEK1 in epithelial cells or fibroblasts was sufficient f

190 horylates ERK2, after the activation loop of MEK1 is itself phosphorylated by Raf.

191 ho family GTPases with ToxB causes a loss of MEK1/2/ERK1/2 signaling and activation of JNK/c-Jun, res

192 An acetyl-mimic of MEK1 increases inappropriate growth properties, suggesti

193 ury- and TNFalpha-induced phosphorylation of MEK1/2 and p38 MAPK in aortic rings, but not of NFkappaB

194 nhibited TNFalpha-induced phosphorylation of MEK1/2 and p38 MAPK in macrophages and endothelial cells

195 cid, induced via CD36 the phosphorylation of MEK1/2-ERK1/2-ETS-like transcription factor-1 cascade, w

196 -characterized negative regulatory region of MEK1.

197 ntate interaction with the Ser212 residue of MEK1.

198 lial apoptosis via concurrent stimulation of MEK1/2 and PI3K but little involvement of MCL-1 and BAD.

199 4, and MKK6 but dispensable for targeting of MEK1, MEK2, and NLRP1B.

200 on of Erk1/2 or pharmacological targeting of MEK1/2 results in supraphysiological activity of the ERK

201 rther increases the nuclear translocation of MEK1.

202 d/bridge/anchor, is a nuclear transporter of MEK1/2-stimulated ERK1/2.

203 rtantly, we demonstrate that combined use of MEK1/2 and Src inhibitors effectively suppresses develop

204 ssion in Tsc1(null) neurons was dependent on MEK1/2 but not mTOR activity, despite both pathways bein

205 BIM phosphorylation was dependent on MEK1/2 kinase activity, and we identified BIM(EL) serine

206 of mono- and doubly phosphorylated forms on MEK1 activity.

207 of melanoma cell lines resistant to BRAF or MEK1/2 inhibitors and enhanced the antineoplastic activi

208 HPV16 E6 or activated mutant HRAS, cRAF1, or MEK1 lost density repression of gamma2 and shared with n

209 inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but not with ERK1/2 inhibitor.

210 o do so in BMDMs lacking the AKT1 isoform or MEK1 and MEK2.

211 No recurrent NRAS, KRAS, or MEK1 mutations were found in 212, 195, or 146 patient sa

212 pearance of secondary NRAS(Q61) mutations or MEK1(Q56P) or MEK1(E203K) mutations.

213 condary NRAS(Q61) mutations or MEK1(Q56P) or MEK1(E203K) mutations.

214 RK pathway as constitutively active B-Raf or MEK1 are able to activate SK1, but constitutively active

215 RK1/2 by small interfering RNA or PD0325901 (MEK1/2 inhibitor) in the tongue and genetic ablation of

216 Phosphorylated MEK1/2 was aberrantly located within the nucleus of prim

217 nduce nuclear accumulation of phosphorylated MEK1/2 and ERK1/2 in intestinal epithelial cells.

218 reases steady-state levels of phosphorylated MEK1/2 in various tumor cells expressing B-Raf(V600E) or

219 ignaling, we show it directly phosphorylates MEK1 (MAP2K1) and that MEK/ERK (MAPK1) signaling is impa

220 nse was mediated through a canonical D1R/PKA/MEK1/2 pathway and independent of ionotropic glutamate r

221 single inhibition of each RTK alone or plus MEK1 inhibitors was ineffective, a combination of inhibi

222 present study shows that PD184161, a potent MEK1/2 inhibitor, is an HIF-1 blocker in Ang II-treated

223 K1/2 dephosphorylation by promoting PP1alpha-MEK1/2 interaction in an ATP-sensitive manner.

224 onal role for mortalin in promoting PP1alpha-MEK1/2 interaction.

225 eta-catenin-dependent signaling by promoting MEK1/2-medidated phosphorylation of LRP5/6 as well as be

226 nic abilities, through a deregulated FAK-Raf-MEK1/2-ERK signaling pathway.

227 moting signaling pathways, PI3K-AKT and Raf1-MEK1-ERK1/2, acting downstream of Ras signaling.

228 lly, mTORC2 acts through Akt to repress Raf1-MEK1/2-ERK1/2 signaling, and inhibition of mTORC2 conseq

229 Inhibition of Ras, MEK1/2 (MAPKK), and ERK1/2, on CTGF-stimulated fibroblas

230 The Ras-MEK1/2-ERK1/2 kinase signaling pathway regulates prolife

231 HB and CRAF in melanoma cells, thus reducing MEK1/2 and ERK1/2 signaling, inhibiting melanoma cell gr

232 mant cells to external stimuli, but requires MEK1/2 inhibition to suppress their survival.

233 ary murine tumors treated with the selective MEK1/2 inhibitor (MEKi) trametinib illustrated a time-co

234 Generation of an acetyl-specific MEK1 antibody demonstrates that endogenous acetylated ME

235 The potent and specific MEK1/2 inhibitor trametinib rapidly blocked ERK1/2 phosp

236 stress promotes a switch to isoform-specific MEK1/ERK2 signaling, induction of GCN2/eIF2alpha phospho

237 nhibiting downstream effectors, specifically MEK1 and/or MEK2 with selumetinib and trametinib (albeit

238 Specifically, MEK1/2 inhibitor treatment up-regulated B1 cell expansio

239 Strikingly, MEK1 appeared to control the asymmetric inheritance of V

240 Paradoxically, this sustained MEK1/2 and ERK1/2 activation was dependent on the active

241 Targeting MEK1/2 is proving to be an important therapeutic strateg

242 Small molecules targeting MEK1/2 and Smoothened hamper proliferation in EphA2-defi

243 ause adhesion is more dependent on KSR1 than MEK1/2.

244 demonstrate that KSR1 has a wider role than MEK1/2 in the development of schwannomas because adhesio

245 We also demonstrate that MEK1/ERK2 signaling pathway is required for nontypeable

246 We further discovered that MEK1/2 inhibition selectively rescued primary glial prog

247 Proteomic analysis evidenced that MEK1 inhibition was accompanied by a sustained activatio

248 ten observed in cancer, we hypothesized that MEK1/2 (MAP2K1/MAP2K2) inhibitors may reduce lactate lev

249 Here, we report that MEK1 and the Nanog-related transcription factor Ventx2 c

250 Collectively, these results show that MEK1/2 inhibition is capable of promoting the reparative

251 The MEK1 kinase directly phosphorylates ERK2, after the acti

252 The MEK1/2 inhibitor, Selumetinib (AZD6244, ARRY-142886) was

253 The MEK1/2 inhibitor, U0126, and mutation of the ERK-depende

254 The MEK1/2 inhibitors U0126 and PD98059 reversed the protect

255 BRAF(V600E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and a

256 2 (TPL-2) (COT, MAP3K8) kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kin

257 molecule PAK1/2/3 inhibitor Frax1036 and the MEK1/2 inhibitor PD0325901, we showed that the combinati

258 Further, the MEK1/2 inhibitor treatment down-regulated pathogenic pro

259 We identified the MEK1/2 pathway as a key regulator of macrophage reparati

260 e number of disease-related mutations in the MEK1 gene that lead to tumorigenesis and abnormal develo

261 We found that mortalin is present in the MEK1/MEK2 proteome and is upregulated in human melanoma

262 g as well as other pathways that include the MEK1/2 module of mitogen-activated protein kinase pathwa

263 ng cascade from activated c-Fms involves the MEK1/2-ERK1/2 pathway.

264 Deletion of the MEK1 gene using LysM(Cre+/+)Mek1(fl/fl) macrophages as a

265 the FcgammaRI receptor and activation of the MEK1-ERK1/2 signaling pathway.

266 These bimodal effects of the MEK1/2 inhibitor treatment on immune responses contribut

267 Bath application of the MEK1/2 inhibitor U0126 did not alter leptin-induced supp

268 Pharmacological inhibition of the MEK1/2 pathway by a MEK1/2 inhibitor (MEKi) significantl

269 apsed ALL, we measured the activation of the MEK1/2 target ERK in matched diagnosis-relapse primary s

270 n of CRAF with subsequent stimulation of the MEK1/2-ERK1/2-Fra1-ZEB1/2 signaling pathway.

271 These studies suggest that the MEK1/2 pathway may be a therapeutic target to promote th

272 ted kinase reactivation are sensitive to the MEK1/2 inhibitor AZD6244/selumetinib or its combination

273 ties increased in MDDCs upon exposure to the MEK1/2 inhibitor U0126.

274 and inhibition of ERK1/2 activation via the MEK1/2 inhibitors U0126 and PD98059 results in decreased

275 are restored when cells are treated with the MEK1/2 inhibitor UO126 or following transfection of the

276 tive than BRAF wild-type cell lines to three MEK1/2 inhibitors tested.

277 Thus, MEK1/2 inhibitors, by targeting the adhesive function of

278 d rapid inhibitory feedback loop from ERK to MEK1, and mediated developmental changes and synaptic ve

279 ced recruitment of GIT1 or MAT2B and ERK2 to MEK1, respectively.

280 irectly promoted binding of GIT1 and ERK2 to MEK1.

281 f and enhance recruitment of Raf proteins to MEK1/2.

282 diverse mechanisms of acquired resistance to MEK1/2 or BRAF inhibitors.

283 ic biomarker for pharmacodynamic response to MEK1/2 inhibition in BRAF-driven cancers.

284 tumors dramatically regressed in response to MEK1/2 inhibition, they regrew following cessation of dr

285 K1 reveals a face-to-face dimer sensitive to MEK1 phosphorylation but insensitive to BRAF dimerizatio

286 ation-dependent manner that was sensitive to MEK1/2 inhibition and V(1A)R inhibition, but not V(1B)R

287 e is responsible for continuous signaling to MEK1/2 and ERK1/2.

288 ding of BRAF V600E but not BRAF wild-type to MEK1 in V600E-positive cancer cells to promote activatio

289 Unlike PD98059, a widely-used MEK1/2 inhibitor, we found that PD184161 blocked AngII-d

290 ly, analysis of these data unveiled the VEGF/MEK1/ERK signaling pathway as a key regulator of the end

291 neurons in vivo and in vitro through VEGFR2, MEK1/2, and inhibition of caspase-3 induction.

292 In vivo, MEK1/2 inhibition prevented TMX-induced cell death in sy

293 T4 ubiquitination was clearly increased when MEK1(CA) was coexpressed and that this increase was more

294 proliferation and induced apoptosis, whereas MEK1 inhibition exerted cytostatic effects.

295 ed CLL cell survival and was associated with MEK1/2 activation and BIM(EL) phosphorylation.

296 treatments targeting Src in combination with MEK1/2 may prevent BC recurrence.

297 structure of the BRAF(KD) in a complex with MEK1 reveals a face-to-face dimer sensitive to MEK1 phos

298 and JNK phosphorylation were inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but

299 r activity or weakening the interaction with MEK1.

300 MAT2B directly interacts with MEK1, GIT1, and ERK2.