ライフサイエンスコーパス: MEK2

1 he activation loop of the MAP kinase kinase, MEK2.

2 bitor of the ERK-activating kinases MEK1 and MEK2.

3 ffect on the interaction with either MEK1 or MEK2.

4 hosphorylate its downstream targets MEK1 and MEK2.

5 st characterized Raf substrates are MEK1 and MEK2.

6 dent or only partially dependent on MEK1 and MEK2.

7 2, although c-Raf can activate both MEK1 and MEK2.

8 e ability to act as a substrate for MEK1 and MEK2.

9 eraction between Cu and the kinases MEK1 and MEK2.

10 RK2, as well as to the MAPK kinases MEK1 and MEK2.

11 RK1/2, the downstream signaling molecules of MEK2.

12 n BMDMs lacking the AKT1 isoform or MEK1 and MEK2.

13 ortical progenitors is regulated by MEK1 and MEK2.

14 ine-threonine kinase that activates MEK1 and MEK2.

15 ed of HSP90, HSP70, HSP68, p50(CDC37), MEK1, MEK2, 14-3-3, and several other, unidentified proteins.

16 ermini of E2 [amino acids (aa) 890-1053] and MEK2 (aa 266-400) were mapped to be crucial for the inte

17 The highly homologous kinases, Mek1 and Mek2, act downstream of Ras and Raf to activate extracel

18 Blocking MEK2 activation does not affect double-strand DNA break

19 We did find that F57C MEK2 activation was less dependent on RAF signaling than

20 ivation of caspase-8, which in turn requires MEK2 activity and secretion of FAS ligand.

21 ancer cells and suggest that tRNA may impact MEK2 activity in cancer cells.

22 ed that copper (Cu) is required for MEK1 and MEK2 activity through a direct Cu-MEK1/2 interaction.

23 Removal of three Mek1/Mek2 alleles or transient post-natal treatment with a lo

24 n of U0126, a specific inhibitor of MEK1 and MEK2, allowing normal terminal erythroid proliferation a

25 MEK1 and MEK2 (also known as MAP2K1 and MAP2K2) are the "gatekeep

26 NRAS, KRAS, MEK1 (also known as MAP2K1) and MEK2 (also known as MAP2K2) mutations.

27 h a selective chemical inhibitor of MEK1 and MEK2 (also known as mitogen-activated protein kinase [MA

28 Interestingly, A-Raf does not activate MEK2, although c-Raf can activate both MEK1 and MEK2.

29 residues that is required for activation of MEK2 and downstream signal propagation.

30 ine kinase TrkA, activated H-Ras, B-Raf, and MEK2 and facilitates their coordinated signaling to prol

31 ockdown of the specific MAPK pathway members MEK2 and MEK4 increased sensitivity to prednisolone thro

32 protein kinase family reveal roles for MEK1/MEK2 and MEKK1, but not p38 or phosphatidylinositol 3-ki

33 Here, we investigate the roles of MEK2 and the MEK2/ERK1/2 cascade in the growth of CSFV f

34 Dominant negative MEK1, MEK2, and ERK2 block PPARgamma-induced EMT, whereas cons

35 The activation of the protein kinases Raf-1, MEK2, and ERK2 is essential for this form of nonapoptoti

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

37 he corresponding sequences in human MEK1 and MEK2 are necessary and sufficient for the direct binding

38 In addition, neither Mek1 nor Mek2 are stably activated in coordination with Raf-1 in

39 Indeed, MEK1 and MEK2 are the only known activators of ERK1 and ERK2.

40 ase kinase 1 (MEK1) and MAP kinase kinase 2 (MEK2) are activated by ionizing radiation.

41 ons, including F53S and Y130C MEK1, and F57C MEK2, are the first naturally occurring mutations to be

42 o kinase assay, which utilized both MEK1 and MEK2 as substrates.

43 This difference results in F57C MEK2 being resistant to the selective RAF inhibitor SB-5

44 g, enhancing MEK1 interaction while reducing MEK2 binding to IQGAP1.

45 Both MEK1 and MEK2 bound IQGAP1 in vitro and coimmunoprecipitated with

46 ly partially reduces recognition by MEK1 and MEK2 but does not promote recognition by other MEKs.

47 by RNA interference directed against ERK2 or MEK2 but not ERK1 or MEK1 and against Nur77.

48 MEK2 but not MEK1 will phosphorylate ERK3.

49 laced in suspension, ERK2 was complexed with MEK2 but not with MEK1.

50 he replication of CSFV, whereas knockdown of MEK2 by lentivirus-mediated small hairpin RNAs dramatica

51 ress stimuli, and because we have shown that MEK2 can affect G2/M checkpoint kinetics, these results

52 mportant for skin tumor development and that Mek2 cannot compensate for the loss of Mek1 function in

53 s in combination was also protective against MEK2 cleavage by lethal toxin or adenylyl cyclase activi

54 lightly inhibited ERK2 activation by RAS and MEK2, co-expression or p70-DeltaC1 or p70-DeltaC2 with e

55 MEK1 and MEK2 contain a proline-rich insert not present in any ot

56 fection of a constitutively active mutant of MEK2 could override the PD098059 blockade.

57 The MEK1 and MEK2 D-sites displayed a strong selectivity for their co

58 ally, the selectivity of the MKK4, MEK1, and MEK2 D-sites for JNK versus ERK was quantified.

59 rh1-1 plants, but cell death triggered by Nt MEK2(DD) was unaffected in CRT1-silenced N. benthamiana,

60 reased the level of HIF-1alpha expression in MEK2-deficient BMDMs and decreased IL-1beta production i

61 Importantly, MEK2-deficient BMDMs exhibited a preserved ERK1/2 phosph

62 -12 production in response to LPS challenge, MEK2-deficient murine bone marrow-derived macrophages (B

63 rn with germ-line mutations in BRAF, MEK1 or MEK2 develop cardio-facio-cutaneous (CFC) syndrome, an a

64 pecific inhibitor for MEK1/2/ERK1/2, whereas MEK2 did not affect CSFV replication after blocking the

65 elia but the expression patterns of MEK1 and MEK2 differed in these lenses.

66 inally, we investigated the role of Mek1 and Mek2 double and triple mutation on ERK phosphorylation,

67 ons had missense mutations in either MEK1 or MEK2, downstream effectors of B-Raf.

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

69 ay and with decreased phosphorylation of the MEK2 effector protein ERK.

70 ted with the down-regulation of genes in the MEK2-ERK pathway and with decreased phosphorylation of t

71 with Vpr, confirming the involvement of the MEK2-ERK pathway in Vpr-mediated cell cycle arrest.

72 ith all three kinase components of the Raf-1/Mek2/Erk signaling module.

73 s of the EGFR pathway (ErbB1 receptor, MEK1, MEK2, ERK1, and ERK2) in A431 cells stimulated with epid

74 s, no mutations within pathway members MEK1, MEK2, ERK1, ERK2, RAP1B, or BAD were found.

75 ed expression of constitutively active MEK1, MEK2, ERK1, or PKCalpha.

76 re, we investigate the roles of MEK2 and the MEK2/ERK1/2 cascade in the growth of CSFV for the first

77 -BP promoter with dominant negative forms of MEK2, extracellular signal-regulated kinase 2, and p38 s

78 5901, a small-molecule inhibitor of MEK1 and MEK2 (factors in the MAPK signaling pathway), along with

79 adial progenitors deficient in both Mek1 and Mek2 fail to transition to the gliogenic mode in late em

80 h potently and selectively degraded MEK1 and MEK2 in a VHL E3 ligase- and proteasome-dependent manner

81 lo syndrome, and mutations in BRAF, MEK1 and MEK2 in cardio-facio-cutaneous syndrome, uncovered the b

82 activated protein kinase kinase 1 (MEK1) and MEK2 in cell growth and proliferation and the kinases UL

83 se mutations reduced LF-mediated cleavage of MEK2 in cell-based assays but altered neither the abilit

84 Our work reveals a novel role of MEK2 in CSFV infection and sheds light on the molecular

85 than 2308, and the attenuation displayed by MEK2 in cultured murine macrophages was enhanced when th

86 sequence of the interaction between tRNA and MEK2 in pancreatic cancer cell lines.

87 ngs demonstrate the interaction of tRNA with MEK2 in pancreatic cancer cells and suggest that tRNA ma

88 tRNA interacts with the wild-type and mutant MEK2 in pancreatic cancer cells; furthermore, the MEK2 i

89 nse germline mutations in the genes MEK1 and MEK2 in patients with CFC.

90 demonstrate a novel regulatory function for MEK2 in response to TLR4 activation in IL-1beta producti

91 ion of wild-type ERK2 with MEK1 but not with MEK2 in serum-starved adherent cells.

92 dy, we examined the requirement for Mek1 and Mek2 in skin neoplasia using the two-step 7,12-dimethylb

93 Currently, little is known about the role of MEK2 in the replication of classical swine fever virus (

94 ogen-activated protein kinase kinase) -1 and MEK2 , in patients with advanced malignancy.

95 f cobimetinib, an oral inhibitor of MEK1 and MEK2, in patients with histiocytoses.

96 ivation through the use of dominant negative MEK2 increases sensitivity of the cell to ionizing radia

97 EMT, whereas constitutively active MEK1 and MEK2 induce a mesenchymal phenotype similar to that evok

98 Although injection of constitutively active MEK2 induced GVBD, treatment with the MEK inhibitors U01

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

100 K inhibitor-induced RTK stimulation overcame MEK2 inhibition, but not MEK1 inhibition, reactivating E

101 t negative mutant MEK1S218/222A and the MEK1/MEK2 inhibitor PD098059.

102 etermine whether the MAPK kinase (MEK) 1 and MEK2 inhibitor selumetinib (AZD6244, ARRY-142886) could

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

104 in pancreatic cancer cells; furthermore, the MEK2 inhibitor U0126 significantly reduces the tRNA-MEK2

105 The specific MEK1/MEK2 inhibitor, PD98059, inhibited extracellular matrix-

106 nib is a selective, orally administered MEK1/MEK2 inhibitor.

107 reated with PD98059, a MAPK/ERK kinase (MEK1/MEK2) inhibitor, displayed a suppression of I/R-induced

108 The E2-MEK2 interaction was confirmed by glutathione S-transfer

109 E207K) to evaluate the function of the tRNA-MEK2 interaction.

110 hibitor U0126 significantly reduces the tRNA-MEK2 interaction.

111 We found that MEK2 is the major kinase, which inversely proportionally

112 Mitogen-activated protein kinase kinase 2 (MEK2) is a kinase that operates immediately upstream of

113 Furthermore, treating cells that coexpressed Mek2-K101A and KGA with suboptimal level of BPTES leads

114 , by both dominant-negative mutants of Mek2 (Mek2-K101A) and K-Ras (K-Ras-S17N) and also by the small

115 ive mutants of Raf-1 (Raf-1-K375M) and Mek2 (Mek2-K101A), protein phosphatase PP2A, and Mek-inhibitor

116 E) phosphorylates and activates the MEK1 and MEK2 kinases, which in turn phosphorylate and activate t

117 y mutations mapping to the BRAF and MEK1 and MEK2 kinases.

118 MEK2 knockdown increased sensitivity to all chemotherapy

119 increases downstream MAP2K1 (MEK1), MAP2K2 (MEK2), MAPK1 (p42 MAPK) and MAPK3 (p44 MAPK) phosphoryla

120 was unimpaired by deletion of either Mek1 or Mek2 MAPKKs individually.

121 stigated the direct contribution of Mek1 and Mek2 MAPKKs to oncogenic Ras signaling.

122 sms, the ATR mechanism and a newly described MEK2 mechanism.

123 tified ERK1/2-inducing mutations in MEK1 and MEK2 (MEK1/2) MAPK genes in melanoma confer resistance t

124 owever, by both dominant-negative mutants of Mek2 (Mek2-K101A) and K-Ras (K-Ras-S17N) and also by the

125 negative mutants of Raf-1 (Raf-1-K375M) and Mek2 (Mek2-K101A), protein phosphatase PP2A, and Mek-inh

126 We demonstrate that LPS also activates MEK2, MEK3, and MEK6.

127 Ser/Thr kinases, such as c-Raf, B-Raf, Mek1, Mek2, Mekk, was not affected by wortmannin.

128 ach of the MAPK kinases (MKKs or MEKs) MEK1, MEK2, MKK3, MKK4, and MKK6.

129 enerated disease and drug resistance-derived MEK2 mutants (Q60P, P128Q, S154F, E207K) to evaluate the

130 lop fewer papillomas than both wild-type and Mek2-null mice following DMBA/TPA treatment.

131 en wild-type, conditional Mek1 knockout, and Mek2-null mice, indicating that Mek1 findings were not d

132 for the G2/M transition, whereas the loss of Mek2 or Erk2 caused arrest at G1.

133 f the ERK cascade (B-Raf and C-Raf, MEK1 and MEK2) or a downstream effector, the transcription factor

134 at activation of ERK8 does not require MEK1, MEK2, or MEK5.

135 Mutations in MEK1, MEK2, or Ste7 that altered conserved residues in the doc

136 LPS stimulation of MEK2 overexpressed in RAW264.7 cells led to a marked dec

137 which the LT proteolytic site was modified: MEK2(P10V/A11D), MEK3(I27D) and MEK6(I15D).

138 Here, we identified a somatic MEK2(P128L) mutation and a germline RUNX1(G60C) mutation

139 The MEK2(P128L) mutation, which has been identified previous

140 en-activated protein kinase (MAPK) kinase 2 (MEK2), p33(Ringo), or Delta 90 cyclin B.

141 protein kinase (MAPK) in the p21(ras)/Raf-1/MEK2 pathway and induced expression of the transcription

142 known IL2-stimulated kinases including MEK1/MEK2 (PD98059), mTOR (rapamycin), and phosphatidylinosit

143 r signal-regulated kinase kinase (MEK) 1 and MEK2, PD98059, and U0126, to assess the role the Ras-mit

144 MEK1 and MEK2 phosphorylate a majority of the ERK2 mutants.

145 We show that MEK2 positively regulates CSFV replication.

146 Taken together, our results indicate that MEK2 positively regulates the replication of CSFV throug

147 and developmental disorders, making Mek1 and Mek2 prime therapeutic targets.

148 Notably, we demonstrate that MEK2 promotes CSFV replication through inhibiting the in

149 in of function experiments by overexpressing MEK2 protein in RAW264.7 cells.

150 talytic activity of the wild type and mutant MEK2 proteins in different ways.

151 e found that mortalin is present in the MEK1/MEK2 proteome and is upregulated in human melanoma biops

152 protein kinase kinase 1 (MAPKK1 (MEK1)) and MEK2 reversed the ability of GE2 to decrease CSR and STA

153 Exogenous provision of excess MEK2 reverses the cell cycle arrest associated with Vpr,

154 , despite the binding of constitutive active Mek2-S222/226D.

155 retaining only one allele of either Mek1 or Mek2 showed intermediate responsiveness.

156 ls and are the first to show a role for MEK1/MEK2 signaling in TREM2 activity.

157 Overexpression of MEK2 significantly promoted the replication of CSFV, whe

158 Furthermore, we found MEK2-SIPK cascade activated while BES1/BZR1 inhibited RB

159 hand, BRs enhanced virus resistance through MEK2-SIPK cascade and RBOHB-dependent ROS burst.

160 To discern MEK1 and MEK2 specificity for their substrate, extracellular sign

161 at least four subgroups in this family; MEK1/MEK2 subgroup that activates ERK1/ERK2, MEK5 that activa

162 the proline-rich sequence (PRS) of MEK1 and MEK2 that is required for constitutive binding to KSR1 a

163 e mitogen-activated protein kinase kinase 2 (MEK2), that interact with tRNA in HEK293T cells.

164 owth (c-Met-related tyrosine kinase (MST1R), MEK2; the guanine nucleotide exchanger RasGRP2, insulin-

165 amatically affected the activity of MEK1 and MEK2 toward ERK2 nor conferred recognition by other MEKs

166 Both Mek1 and Mek2 triggered ERK phosphorylation.

167 vated protein (MAP) kinase kinases, MEK1 and MEK2, two MAP kinases, NTF6 and wound-induced protein ki

168 In contrast, MEK2 was elevated by only 28%.

169 In this study, MEK2 was identified as a novel binding partner of the E2

170 % of MAPK but none of MAPK kinase (MEK1A and MEK2) was microtubule bound.

171 An isogenic sodC mutant, designated MEK2, was constructed from B. abortus 2308 by gene repla

172 tively active form of the MAP kinase kinase, MEK2, was sufficient to induce HIF-1 alpha protein and V

173 igate functional redundancy between Mek1 and Mek2, we disrupted these genes in murine and human epide

174 or BMDM from targeted deficiency in MEK1 and MEK2, we show that rapamycin treatment led to an increas

175 xperiments confirmed that decreased MEK1 and MEK2 were required for this recruitment.

176 ybrid interaction of ERK2 with both MEK1 and MEK2, whereas others had a predominant effect on the int

177 nced by fourfold the in vitro interaction of MEK2 with IQGAP1 without altering binding of MEK1.

178 wnstream effectors, specifically MEK1 and/or MEK2 with selumetinib and trametinib (albeit with poor t