ライフサイエンスコーパス: MEK1

1 MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) are the

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

3 MEK1 has recently been shown to translocate to the nucle

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 reduces the nuclear level of SMRT in an activation-

8 MEK1 was required to make Xenopus pluripotent cells comp

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

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

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

12 MEK1/2 can be activated by numerous molecules including

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

14 e mitogen-activated protein kinase kinase 1 (MEK1) enzyme (psMEK) short-circuits the highly conserved

15 d mitogen-activated protein kinase kinase 1 (MEK1)-silenced cells showed a decrease in the number of

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

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

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

19 1 murine leukemia viral oncogene homolog 1), MEK1/2 (mitogen-activated protein kinase or ERK kinase 1

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

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

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

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

24 mitogen-activated protein kinase kinase 1/2 (MEK1/2), but not extracellular regulated kinase 1/2, cau

25 e II (CaMKII), Raf, and MAPK/ERK kinase 1/2 (MEK1/2).

26 en-activated protein kinase kinases 1 and 2 (MEK1/2) degrader, MS432.

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

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

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

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

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

32 We used TRACE in a MEK1 inhibitor-resistance screen, and identified functio

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

34 med to assess the activity of selumetinib, a MEK1/2 inhibitor, in these patients.

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

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

37 es subsets of genes dysregulated by aberrant MEK1/2 or ERK5 pathways that could contribute to the NS-

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

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

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

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

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

43 rying cardiac-specific constitutively active MEK1 (TnT-MEK1-CA) was administrated to rescue cardiac d

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

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

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

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

48 ich could be rescued by expression of active MEK1.

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

50 1 constitutive activity, but how they affect MEK1 regulation and function remains largely unknown.

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

52 erize E6201 as a dual inhibitor of ACVR1 and MEK1/2, and demonstrate its efficacy toward tumor cells

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

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

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

56 driven by mutations mapping to the BRAF and MEK1 and MEK2 kinases.

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

58 BRAF and MEK1/2 inhibitors are effective in melanoma but resistan

59 d confirm its impact in BRAF, EGFR, HER2 and MEK1.

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

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

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

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

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

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

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

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

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

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

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

71 posure levels in mice, representing the best MEK1/2 degrader to date for in vivo studies.

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

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

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

75 The reconstruction reveals an inactive BRAF-MEK1 complex restrained in a cradle formed by the 14-3-3

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

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

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

79 homeostatic regulation of T cell function by MEK1.

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

81 432N (24), and its effect was phenocopied by MEK1/2 knockdown.

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

83 ural-cell-derived CCL2 stimulates tumor cell MEK1-ERK1/2-ROCK2-dependent signaling and enhances tumor

84 e to genetic ablation of NRAS or combination MEK1/2 and CDK4/6 inhibition by upregulating activity of

85 unctional inhibitor strategy toward combined MEK1/PI3K inhibition.

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

87 Concurrent MEK1 and PI3K inhibition was demonstrated with inhibitor

88 er protein-interacting pairs, including CRAF-MEK1, RIT1-RGL3, and p53-MDM2.

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

90 r MEK1 and MEK2 activity through a direct Cu-MEK1/2 interaction.

91 ockdown experiments confirmed that decreased MEK1 and MEK2 were required for this recruitment.

92 23), which potently and selectively degraded MEK1 and MEK2 in a VHL E3 ligase- and proteasome-depende

93 compounds potently and selectively degraded MEK1/2 by hijacking the ubiquitin-proteasome system, inh

94 against oncogenic BRAF and/or the downstream MEK1/2 kinases.

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

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

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

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

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

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

101 latory helix of the MAP2K1 gene encoding for MEK1.

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

103 discovered that copper (Cu) is required for MEK1 and MEK2 activity through a direct Cu-MEK1/2 intera

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

105 d cells and are the first to show a role for MEK1/MEK2 signaling in TREM2 activity.

106 Compound 23 was highly selective for MEK1/2 in global proteomic profiling studies.

107 lation event is necessary and sufficient for MEK1 activity.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

122 ndothelial cell dysfunction due to increased MEK1 activity.

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

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

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

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

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

128 C cell that is context specific and involves MEK1/2/pERK1/2, MEK5/pERK5, PI3K, and nuclear factor kap

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

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

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

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

133 tive mitogen-activated protein kinase kinase MEK1/2, MEK5, and phosphoinositide 3-kinase (PI3K) inhib

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

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

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

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

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

139 ile inhibitors of the ERK activating kinases MEK1/2 are promising as a means to treat NF1, the broad

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

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

142 Inhibitors of the kinases MEK1/2 displayed the strongest and most consistent incre

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

144 patients with ARAF, BRAF, RAF1, NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2

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

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

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

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

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

150 istance to MEK and PI3K inhibitors observed, MEK1/2 mutation or loss of PTEN, are similar to those de

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

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

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

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

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

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

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

158 rader 27, suggesting that the combination of MEK1/2 degradation with BRAF or PI3K inhibition may prov

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

160 Here, we report a first-in-class degrader of MEK1/2, MS432 (23), which potently and selectively degra

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

162 have identified a novel nuclear function of MEK1.

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

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

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

166 1 signaling by pharmacological inhibition of MEK1 kinase in Huh7 cells caused de-repression of CYP3A4

167 Combinatorial inhibition of MEK1/2 and CDK4/6 is currently undergoing clinical inves

168 inhibitors, we found that dual inhibition of MEK1/2 and insulin-like growth factor 1 receptor (IGF1R)

169 elanoma models, due in part to inhibition of MEK1/2 kinase activity.

170 Mechanistically, inhibition of MEK1/2 leads to activation of the LKB1->AMPK->ULK1 signa

171 Furthermore, combined inhibition of MEK1/2 plus autophagy displays synergistic anti-prolifer

172 Pharmacological inhibition of MEK1/2 specifically inhibited proliferation and sensitiz

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

174 odulation of resistance to the inhibition of MEK1/2, CDK4/6, or their combination in NRAS-mutant mela

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

176 ondrial inhibition rather than inhibition of MEK1/2.

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

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

179 l trial of cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses.

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

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

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

183 tors of resistance to clinical inhibitors of MEK1/2 and CDK4/6 alone and in combination.

184 Inhibitors of MEK1/2, the kinases upstream of ERK1/2, have been critic

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

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

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

188 1 transcriptional activity is a mechanism of MEK1/2 inhibition resistance in RAS-driven neuroblastoma

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

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

191 d by VEGF that results in phosphorylation of MEK1/ERK and activation of ERG leading to expression of

192 -characterized negative regulatory region of MEK1.

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

194 4, and MKK6 but dispensable for targeting of MEK1, MEK2, and NLRP1B.

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

196 Pharmacological co-targeting of MEK1/2, HDAC3, and G9a sustains PDAC tumor growth inhibi

197 rther increases the nuclear translocation of MEK1.

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

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

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

201 cells evolved to be resistant to BRAF and/or MEK1/2 inhibitors, combined treatment with TTM and the c

202 nt targeted therapies against mutant BRAF or MEK1/2 have been hindered by existence of innate or deve

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

204 Consequently, BRAF or MEK1/2 inhibitors are synthetic lethal with the MCL1 inh

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

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

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

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

209 Pharmacological inhibition of Rac1 or MEK1/2 reduced P-Rex1-driven tumoroid formation and cell

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

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

212 izing perturbed signaling network with PI3K, MEK1/2 and AMPK inhibitors.

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

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

215 study was to evaluate binimetinib, a potent MEK1/2 inhibitor with demonstrated activity across multi

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

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

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

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

220 relatively protracted activation of the RAF-MEK1/2-ERK1/2 module, in comparison with RAF1 membrane l

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

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

223 nd 27 (MS934), and the first CRBN-recruiting MEK1/2 degrader 50 (MS910).

224 sulted in two novel, improved VHL-recruiting MEK1/2 degraders, 24 (MS928) and 27 (MS934), and the fir

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

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

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

228 s regulating VE-cadherin, we stably silenced MEK1 and observed that VEGF was no longer able to induce

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

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

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

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

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

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

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

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

237 Targeting MEK1/2 sensitizes AML blasts to genotoxic agents, indica

238 MAPK signaling can be inhibited by targeting MEK1/2; unfortunately, this approach has been largely in

239 Numerous inhibitors targeting MEK1/2 have been developed including three FDA-approved

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

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

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

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

244 We found that MEK1/2 inhibition (MEKi) induces T(SCM) that have naive

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

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

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

248 The MEK1 kinase directly phosphorylates ERK2, after the acti

249 The MEK1/2 inhibitor trametinib delays tumor growth but does

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

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

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

253 2 (TPL-2) (COT, MAP3K8) kinase activates the MEK1/2-extracellular-signal regulated kinase 1/2 MAP kin

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

255 selective BRAF inhibitor dabrafenib and the MEK1/2 inhibitor trametinib in patients with solid tumor

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

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

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

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

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

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

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

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

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

265 Jun protein that follows inactivation of the MEK1/2-Erk1/2 signaling pathway.

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

267 ETV5 in cells treated with either LT or the MEK1/2 inhibitor, U0126.

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

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

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

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

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

273 t with adeno-associated virus serotype 9 TnT-MEK1-CA nearly abolished the detrimental phenotype of kn

274 iac-specific constitutively active MEK1 (TnT-MEK1-CA) was administrated to rescue cardiac dysfunction

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

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

277 irectly promoted binding of GIT1 and ERK2 to MEK1.

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

279 ETD5 as a major driver of PDAC resistance to MEK1/2 inhibition (MEKi).

280 Acquired resistance to MEK1/2 inhibitors (MEKi) arises through amplification of

281 However, acquired resistance to MEK1/2 inhibitors has been observed in patients, and new

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

285 t on NRAS for proliferation and sensitive to MEK1/2 and CDK4/6 combination treatment.

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

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

288 To date, only two MEK1/2 degrader papers have been published and very limi

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

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

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

296 ctures of full-length BRAF in complexes with MEK1 and a 14-3-3 dimer.

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

298 r activity or weakening the interaction with MEK1.

299 ling was interrogated pharmacologically with MEK1/2 inhibitor U0126 or genetically with bone marrow-d

300 mutant Bliley TCC cells and synergized with MEK1/2 inhibition in Bliley and BRAF wild-type Kinsey ce