ライフサイエンスコーパス: MEK2

1 RK2, as well as to the MAPK kinases MEK1 and 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 RK1/2, the downstream signaling molecules of MEK2.

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

11 ortical progenitors is regulated by MEK1 and MEK2.

12 ine-threonine kinase that activates MEK1 and MEK2.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

43 MEK2 but not MEK1 will phosphorylate ERK3.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

69 5901, a small-molecule inhibitor of MEK1 and MEK2 (factors in the MAPK signaling pathway), along with

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

97 hibitor U0126 significantly reduces the tRNA-MEK2 interaction.

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

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

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

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

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

103 MEK2 knockdown increased sensitivity to all chemotherapy

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

126 We show that MEK2 positively regulates CSFV replication.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

145 Both Mek1 and Mek2 triggered ERK phosphorylation.

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

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

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

149 % of MAPK but none of MAPK kinase (MEK1A and MEK2) was microtubule bound.

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

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

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

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

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

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

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