ライフサイエンスコーパス: MEKK1

1 MEKK1 ablation or down-regulation by interfering RNA sig

2 MEKK1 also has the capacity to activate IKK, the central

3 MEKK1 also prevents apoptosis and inflammation, thereby

4 MEKK1 also regulates Fra-2 protein stability by inducing

5 MEKK1 becomes phosphorylated on multiple sites and polyu

6 MEKK1 deficiency causes loss of vinculin in focal adhesi

7 MEKK1 encodes a MAP kinase kinase kinase and is a member

8 MEKK1 has a plant homeobox domain (PHD) that has been sh

9 MEKK1 induced AR-dependent apoptosis in prostate cancer

10 MEKK1 inhibits MyoD-directed transcriptional activity wi

11 MEKK1 is a MAPK kinase kinase that is activated in respo

12 MEKK1 is a MAPKKK that regulates both the extracellular

13 MEKK1 is a mitogen-activated protein kinase (MAPK) kinas

14 MEKK1 is a mitogen-activated protein kinase kinase kinas

15 MEKK1 is activated in response to growth factors and cyt

16 MEKK1 is associated with actin fibers and focal adhesion

17 MEKK1 is comprised of a kinase domain and a long amino-t

18 MEKK1 is required for activation of the cysteine proteas

19 MEKK1 kinase activity is required for ubiquitylation of

20 MEKK1 may play a structural role in signaling, independe

21 MEKK1 phosphorylates and activates MKK1 and MKK4, leadin

22 MEKK1 phosphorylation on Thr(1381) is observed during Th

23 MEKK1 regulates AP-1-dependent gene expression by regula

24 MEKK1 signaling regulates migration through control of c

25 MEKK1 strongly stimulated recruitment of polyQ polypepti

26 MEKK1 TOG demonstrates a clear preference for binding cu

27 MEKK1 ubiquitylation is inhibited by mutation of cystein

28 MEKK1 ubiquitylation represents a mechanism for inhibiti

29 MEKK1 was recruited to CD40 and adaptor molecule TRAF2 a

30 MEKK1, a kinase that can physically associate with Raf,

31 MEKK1-deficient mice show an eye open at birth phenotype

32 MEKK1-deficient mice with mammary gland-targeted express

33 MEKK1-dependent signaling regulates HECT E3 ligase Itch,

34 MEKK1-driven JNK activation is required for actin stress

35 MEKK1-induced apoptosis is amplified by blocking PI-3 ki

36 s mitogen-activated protein kinase kinase 1 (MEKK1) in a G(i)-Ras-dependent manner and that MEKK1 act

37 MEK kinase 1 (MEKK1) induces apoptosis through the activation of caspa

38 Recombinant forms of MAP3K MEK kinase 1 (MEKK1) interact in vivo and in vitro with the STE20 prot

39 MAPK/ERK kinase kinase 1 (MEKK1) is a mitogenactivated protein kinase kinase kinas

40 MEK kinase 1 (MEKK1) is highly expressed in the growing tip of the eye

41 ivated protein kinase kinase (MEK) kinase 1 (MEKK1) mediates activin B signals required for eyelid ep

42 a mitogen and extracellular kinase kinase 1 (MEKK1) mutant or lacking JNK1 or the E3 ubiquitin ligase

43 hat both JNK isoforms transmit MEK kinase 1 (MEKK1)-mediated morphogenetic signals during mouse embry

44 en-activated protein kinase kinase kinase 1 (MEKK1)/c-Jun-NH(2)-kinase (JNK) pathway represses hTR ex

45 Kinases (MEK1/2), MAPK/ERK Kinase Kinase-1 (MEKK1), extracellular signal-regulated kinase (ERK), and

46 er TPA, anisomycin and MAPK kinase kinase-1 (MEKK1), phosphorylated Nur77 and induced its nuclear exp

47 endogenous cardiac MAPK/ERK kinase kinase-1 (MEKK1)/(MAP3K1), a mitogen-activated protein kinase kina

48 with dominant negative forms of Ras, Raf-1, MEKK1, MEK1, MEK3, MEK7, ERK2, JNK1, and p38/RK inhibit

49 We propose that PKCdelta activates a MEKK1/MEK3/p38delta MAPK cascade to increase p53 levels

50 propose a RhoA-ROCK-MEKK1-JNK pathway and a MEKK1-p38 pathway as Smad-independent mechanisms in the

51 kinase kinase 1) mutation and also carried a MEKK1 rescue construct.

52 e opposite effect induced by expression of a MEKK1 PHD/RING finger domain mutant were consistent with

53 We propose that a MEKK1-JNK1/2 axis governs the JNK activation levels to c

54 activate JNK following stimulation through a MEKK1/MKK4/MKK7 pathway, resulting in greater cardiac nu

55 sitol 3-kinase (PI3-K) inhibitor accelerated MEKK1-induced Nur77 nuclear export.

56 that purified, active GCK and TRAF2 activate MEKK1.

57 itor SP600125 and was repressed by activated MEKK1.

58 E3 ligase Itch is recruited to activated MEKK1, but not MEKK2, and this novel scaffolding interac

59 Once activated, MEKK1 phosphorylates the MAP2K MKK4, which in turn phosp

60 Forced oligomerization also activates MEKK1, and GCK elicits enhanced oligomerization of coexp

61 ved that coexpression of constitutive-active MEKK1 inhibited TR3 transcriptional activity and TR3-ind

62 -9-dependent cleavage of c-Jun at Asp-65 and MEKK1-mediated ubiquitylation and degradation of c-Jun i

63 of inhibitory kappaB kinase (IKK)-alpha, and MEKK1 mediated the activation of IKK complex, including

64 strogen receptor activation by estrogens and MEKK1.

65 transcriptional activation by estrogens and MEKK1.

66 Expression and MEKK1-mediated threonine 288 phosphorylation of CNN-3 is

67 rminal center kinase (GCK), and both GCK and MEKK1 associate in vivo with the adapter protein tumor n

68 Here we show that endogenous GCK and MEKK1 associate in vivo.

69 kinase family reveal roles for MEK1/MEK2 and MEKK1, but not p38 or phosphatidylinositol 3-kinase.

70 f Muc4/SMC by PEA3 is potentiated by Ras and MEKK1 kinases.

71 t to the TNFR1 complex and decreased Ras and MEKK1/2 activation.

72 at includes protein kinase C (PKC), Ras, and MEKK1 regulates involucrin (hINV) gene expression in epi

73 ibits the novel protein kinase C-, Ras-, and MEKK1-dependent activation of hINV promoter activity and

74 ylation that involves activation of RhoA and MEKK1, phosphorylation and degradation of IkappaB, relea

75 on between the SH3 domain of p115 RhoGAP and MEKK1 and results in activation of ERK1/2.

76 nofluorescence, and K63Ub-modified TRAF6 and MEKK1 in vitro and ex vivo.

77 cascade include the orthologs of Arabidopsis MEKK1 and tomato MAPKKKalpha.

78 Those defects were B cell intrinsic, as MEKK1 was necessary for CD40-mediated activation of the

79 r, JNK1 and JNK2 are not synonymous, because MEKK1 is haploinsufficient for normal eyelid closure in

80 AKT did not, however, block MEKK1-induced JNK activation, showing that regulation of

81 Inhibitors that block MEKK1 downstream pathways, including MEK1/2, MKK4/7, and

82 ation and overexpression of AKT blocked both MEKK1-induced apoptosis and caspase activation.

83 addition, ATF3 promoter can be activated by MEKK1, an upstream activator of the ERK and JNK kinase p

84 asis for the regulation of eyelid closure by MEKK1.

85 gulatory factors, is severely compromised by MEKK1-initiated signaling.

86 ow inducible uPA expression is controlled by MEKK1, a MAPK kinase kinase that regulates the ERK1/2 an

87 ing overcame the negative effects exerted by MEKK1 on the amino terminus of E47.

88 Induction of Nur77 nuclear export by MEKK1 required a prolonged MEKK1 activation and was atte

89 )/Ser(363), and this effect was inhibited by MEKK1 siRNA and PD98059.

90 IL-8/CXCL8-luciferase were also inhibited by MEKK1 siRNA, PD98059 (an MEK inhibitor), U0126 (an ERK i

91 BPbeta-luciferase activity were inhibited by MEKK1 siRNA, PD98059, and RSK1 siRNA.

92 increase in ERK activation was inhibited by MEKK1 siRNA.

93 CTGF promoter is antagonized by c-Jun or by MEKK1, suggesting that a proper balance between the Ras/

94 howing that regulation of the JNK pathway by MEKK1 is independent of its role in regulation of apopto

95 alone but were extensively down-regulated by MEKK1 plus the progestin R5020.

96 Repression by MEKK1 was blocked by SP600125 or enhanced by coexpressio

97 4 but does not appear to be ubiquitinated by MEKK1 under conditions that result in modification of ER

98 PR protein levels were unchanged by MEKK1 alone but were extensively down-regulated by MEKK1

99 dentify a complete plant MAP kinase cascade (MEKK1, MKK4/MKK5 and MPK3/MPK6) and WRKY22/WRKY29 transc

100 he mitogen-activated protein kinase cascade: MEKK1, -2, or -4 for MAP kinase kinase kinase; MKK4 and/

101 or several divergent kinases including Cdc5, MEKK1, GRK2 and Pto.

102 cits enhanced oligomerization of coexpressed MEKK1 in vivo.

103 After TCR costimulation, MEKK1 predominantly induces JNK1 activation, whereas the

104 xpressing activated Raf and kinase-defective MEKK1 remain differentiation-defective, suggesting that

105 Delayed MEKK1-dependent tumor dissemination is associated with m

106 ive enrichment of tumor cells with disrupted MEKK1-microtubule association.

107 sion of dominant negative versions of either MEKK1 or MEKK4 effectively blocks both the activation of

108 on also prevented the cleavage of endogenous MEKK1 by genotoxins.

109 he level of c-myc deletion mutants following MEKK1 expression.

110 Increased c-Myc stability following MEKK1/JNK stimuli is abolished upon mutation within the

111 urified proteins and suggest a mechanism for MEKK1 activation involving induced oligomerization and c

112 The mechanism for MEKK1-induced apoptosis involves caspase-mediated cleava

113 o acids 127-189 was found to be required for MEKK1-dependent increase in c-myc stability.

114 persensitive response, suggesting a role for MEKK1 kinase activity in this aspect of plant disease re

115 We have found MEKK1 to be necessary for uPA up-regulation in response

116 The signal linkage map from MEKK1/MEKK4 to MEK1/MKK4 to JNK is obligate in this G al

117 in keratinocytes from wild-type but not from MEKK1-deficient mice.

118 The Arabidopsis (Arabidopsis thaliana) gene MEKK1 encodes a mitogen-activated protein kinase kinase

119 ation of SAPK through a Lyn --> PKCdelta --> MEKK1 --> MKK7 --> SAPK signaling cascade in response to

120 Herein, we define how MEKK1, a MAPK kinase kinase, regulates cell migration.

121 However, MEKK1 ablation does not impair other TGF-beta/activin fu

122 However, MEKK1-/- mice display significantly delayed tumor cell d

123 ase kinase kinase (MAPKKK) homologs of human MEKK1 in pathogen-resistance pathways.

124 ty of AKT/PKB (AKT) to inhibit cell death in MEKK1-induced apoptosis.

125 The AR acetylation mutant was defective in MEKK1-induced apoptosis, suggesting that the conserved A

126 overloaded hearts by using mice deficient in MEKK1.

127 Upregulation of JunB expression in MEKK1-/- cells forms an inhibitory AP-1 complex that bin

128 JunB mRNA is significantly increased in MEKK1-/- cells, demonstrating that MEKK1 suppresses JunB

129 2 activation and chemotaxis are inhibited in MEKK1-/- fibroblasts.

130 rment in c-Jun N-terminal phosphorylation in MEKK1-deficient mice.

131 tent with a higher level of c-Jun protein in MEKK1(-/-) cells than in corresponding wild-type cells.

132 ting that tubulin binding may play a role in MEKK1 activity at the cellular periphery.

133 Overexpression of kinase inactive MEKK1 inhibits MEKK1-mediated apoptosis and effectively

134 DcR1) and dominant negative FADD, we inhibit MEKK1-induced apoptosis.

135 expression of kinase inactive MEKK1 inhibits MEKK1-mediated apoptosis and effectively blocks death re

136 ation within the kinase domain and an intact MEKK1 RING finger motif.

137 rmation with a construct carrying the intact MEKK1 gene.

138 Of interest, MEKK1 immunoprecipitates from IL-1-stimulated FLS appear

139 n IFN-gamma-stimulated pathway that involves MEKK1-MEK1-ERK1/2 kinases to regulate C/EBP-beta-depende

140 Furthermore, expression of 91 kDa MEKK1 increased DR4 and FAS mRNA and protein levels.

141 In cultured keratinocytes, MEKK1 is essential for JNK activation by TGF-beta and ac

142 ctivated protein kinase (MAPK) kinase kinase MEKK1 upon ligation.

143 ation is dependent on the MAPK kinase kinase MEKK1.

144 kinases in the regulation of the MAP3 kinase MEKK1 and the potential impact on signaling to MAP kinas

145 proteins and in the cellular protein kinase MEKK1 (mitogen-activated protein kinase/extracellular si

146 s to function upstream of the protein kinase MEKK1 in the SAPK pathway.

147 Mice lacking activity of the kinase MEKK1 ('Map3k1(deltaKD)' mice) have defective activation

148 mobility, their association with the kinase MEKK1, and activation of the JNK/p38/NFkappaB pathway.

149 ogen-activated protein kinase kinase kinase (MEKK1) mediates activation of c-Jun NH(2)-terminal kinas

150 he induction of apoptosis by the JNK kinase, MEKK1.

151 ogen-activated protein kinase kinase kinase, MEKK1, leading to the stimulation of the NF-kappaB signa

152 timulates the kinase activity of full-length MEKK1 as much as 10-fold toward MEK4 but does not appear

153 actin fibers and focal adhesions, localizing MEKK1 to sites critical in the control of cell adhesion

154 Unlike the other MAP3Ks, MEKK1 (encoded by Map3k1) contains a PHD motif.

155 siRNA-mediated MEKK1 knockdown inhibits uPA activity, cell migration an

156 VIII of the protein kinase domain of MEKK1 (MEKK1 Delta) differentially affect its ability to activa

157 of ERK1/2 or calpain, but not of JNK, mimics MEKK1 deficiency.

158 A dominant negative MEKK1 blocks C/EBP-beta-driven gene expression stimulate

159 KK1 gene or expressing the dominant negative MEKK1, ERK activation, and GATE dependent gene expressio

160 ominant negative H-Ras, or dominant negative MEKK1.

161 of PKG were inhibited by a dominant negative MEKK1.

162 criptional activity induced by MEKK3 but not MEKK1 and MEK4.

163 K2, TAK1, and trace amounts of MEKK3 but not MEKK1 or apoptosis-signal regulating kinase-1.

164 ibition of TAK1 also impaired MEKK3 (but not MEKK1) activation by fMLF.

165 Notably, MEKK1 activity is triggered by microtubule-targeting che

166 ubiquitylation and preserves the ability of MEKK1 to catalyze MKK1 and MKK4 phosphorylation.

167 Expression of WWOX attenuates the ability of MEKK1 to increase the activity of a c-Jun-driven activat

168 determinants responsible for the ability of MEKK1 to recognize specific substrates are poorly unders

169 In mice, the absence of MEKK1 abolished the increase in cardiac mass, myocyte si

170 uired for complex assembly and activation of MEKK1 and MAPK cascades.

171 Activation of MEKK1 can trigger various responses, including mitogen-a

172 However, constitutive activation of MEKK1 dramatically inhibits biochemical and morphologica

173 ation and JNK activation tuned activation of MEKK1 during osmotic stress, leading to junction dissoci

174 se results represent the first activation of MEKK1 in vitro using purified proteins and suggest a mec

175 We report here that whereas activation of MEKK1 leads to phosphorylation of SMRT, its dissociation

176 necessary for optimal in vitro activation of MEKK1, but the kinase domain of GCK is not.

177 1 (K361M) showed that the kinase activity of MEKK1 may not be required for flg22-induced MPK4 activat

178 Both cleavage of MEKK1 and increased expression of death receptor 4 (DR4,

179 ptosis involves caspase-mediated cleavage of MEKK1, releasing a pro-apoptotic 91 kDa kinase fragment

180 promoter induction, whereas coexpression of MEKK1 with Sp3 enhanced hTR promoter repression.

181 ted protein (MAP) kinase cascade composed of MEKK1, MKK1/MKK2, and MPK4 was previously described as a

182 The functional consequence of MEKK1 ubiquitylation is the inhibition of MEKK1 catalyze

183 immune-activated MAPK cascade, consisting of MEKK1, MKK1/2, and MPK4, triggers cell death and autoimm

184 The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun

185 m cells in culture, homozygous disruption of MEKK1 selectively impaired c-Jun N-terminal kinase activ

186 bdomain VIII of the protein kinase domain of MEKK1 (MEKK1 Delta) differentially affect its ability to

187 degradation by the PHD/RING finger domain of MEKK1, which exhibited E3 ubiquitin ligase activity towa

188 Pases interact with the regulatory domain of MEKK1.

189 ctly phosphorylated the N-terminal domain of MEKK1.

190 Because signal transfer downstream of MEKK1 may involve several MAPK kinases (MEKs), it is imp

191 The inhibitory effect of MEKK1 was mediated through activation of Jun N-terminal

192 e activation of JNK by ectopic expression of MEKK1 induced p75NTR cleavage and cell death.

193 Expression of MEKK1, an upstream regulator of protein kinases that has

194 tably, a large portion of the active form of MEKK1 was associated with the insoluble fraction, concen

195 This function of MEKK1 requires kinase activity, as the kinase-dead mutan

196 impinge upon the regulation and function of MEKK1.

197 orylated and activated NHE1 independently of MEKK1.

198 of MEKK1 ubiquitylation is the inhibition of MEKK1 catalyzed phosphorylation of MKK1 and MKK4 resulti

199 and is blocked by AKT through inhibition of MEKK1 cleavage.

200 inase activity, as the kinase-dead mutant of MEKK1 cannot stimulate this process.

201 oxin C3 and by a dominant negative mutant of MEKK1.

202 The C441A mutation within the PHD of MEKK1 prevents ubiquitylation and preserves the ability

203 ing as a molecular beacon for recruitment of MEKK1, which in turn mediates dismissal of the N-CoR/HDA

204 The present study investigates the role of MEKK1 in epithelial wound healing, another activin-regul

205 se PAK1 phosphorylates the amino terminus of MEKK1 on serine 67.

206 to a site in the aminoterminal one-third of MEKK1, which includes its PHD domain.

207 K1 and JNK activity and that transfection of MEKK1 into knockout cells restores inducible uPA express

208 it defective non-canonical ubiquitination of MEKK1 and TAB1.

209 e activity is required for ubiquitylation of MEKK1.

210 targets additional component(s) upstream of MEKK1 in the MEKK1-MKK1/2-MPK4 cascade and the plasma me

211 performed using a kinase-impaired version of MEKK1 (K361M) showed that the kinase activity of MEKK1 m

212 ults provide evidence that subdomain VIII of MEKK1 is involved not only in binding to, but also in di

213 ovel scaffolding interaction is dependent on MEKK1 Thr(1381) phosphorylation within the kinase domain

214 tivates JNK through a mechanism dependent on MEKK1, it phosphorylated and activated NHE1 independentl

215 n of uPA expression is strongly dependent on MEKK1.

216 radiation, and PKC, but not by anisomycin or MEKK1.

217 Falpha-induced JNK and MKK4 (but not MKK7 or MEKK1) activation, whereas prior exposure to a p38-activ

218 selective inhibitors for p160(ROCK), PKC, or MEKK1.

219 n of PKCdelta, constitutively active Ras, or MEKK1.

220 Jun NH(2)-terminal kinase signaling pathway (MEKK1, MEK4, and JNK1/2) was unchanged, but expressions

221 ssion of constitutively active Akt prevented MEKK1-induced Nur77 nuclear export.

222 nuclear export by MEKK1 required a prolonged MEKK1 activation and was attenuated by Akt activation.

223 verexpression of upstream MAPKs such as Raf, MEKK1, TAK1-DeltaN, and ASK1 up-regulated the transactiv

224 e a unique shift in MAPK activity via a Ras, MEKK1, MEK3 pathway, to increase p38 delta and inhibit E

225 iation marker, involucrin (hINV), via a Ras, MEKK1, MEK3, p38delta signaling cascade.

226 A protein kinase C, Ras, MEKK1, MEK3 signaling cascade controls hINV expression b

227 es the novel protein kinase C isoforms, Ras, MEKK1, MEK3, and a p38delta-extracellular signal regulat

228 inhibited by dominant-negative forms of Ras, MEKK1, MEK3, and p38.

229 via a protein kinase Cdelta (PKCdelta), Ras, MEKK1, MEK3 cascade that increases AP1 factor level and

230 the signaling pathway consisting of G(i)-Ras-MEKK1 mediated LPA-induced FAK membrane redistribution b

231 o showed that the disruption of the G(i)-Ras-MEKK1 pathway led to a significant reduction in LPA-stim

232 Our studies thus suggest that the G(i)-Ras-MEKK1 signaling pathway mediates LPA-stimulated ovarian

233 ted with JNK activity, as MarvelD3 recruited MEKK1 to junctions, leading to down-regulation of JNK ph

234 se pathways, a function that may not require MEKK1's full kinase activity.

235 rowth factor-induced uPA expression requires MEKK1-dependent MKK1 and JNK activity and that transfect

236 to MEKK1 activation, we propose a RhoA-ROCK-MEKK1-JNK pathway and a MEKK1-p38 pathway as Smad-indepe

237 skin wound model, injury markedly stimulates MEKK1 expression and activity, which are in turn require

238 KK1) in a G(i)-Ras-dependent manner and that MEKK1 activity is essential for LPA-stimulated ovarian c

239 Therefore, we conclude that MEKK1 expression is required for PMA- or FGF-2-induced s

240 These results demonstrate that MEKK1 plays a key role in transducing the l-Glu signal t

241 Herein, we demonstrate that MEKK1 regulates the AP-1 protein repertoire.

242 Recently, we have demonstrated that MEKK1 binds to p115 Rho GTPase-activating protein, which

243 stern blot analysis of FLS demonstrated that MEKK1, MEKK2, and TAK1 were readily detectable and were

244 reased in MEKK1-/- cells, demonstrating that MEKK1 suppresses JunB mRNA expression.

245 Our data emphasize that MEKK1 is an essential component of signaling cascades ne

246 Our results indicate that MEKK1 acts upstream of MPK4 as a negative regulator of p

247 rrying T-DNA knockout alleles indicated that MEKK1 is required for flg22-induced activation of MPK4 b

248 ar to wild-type littermates, indicating that MEKK1 deficiency does not affect PyMT-mediated transform

249 /+) but not Mekk1(-/-) mice, indicating that MEKK1 mediates JNK activation by pressure overload.

250 Here we show that MEKK1 contains a previously unidentified tumor overexpre

251 We also show that MEKK1 mutations at the tubulin-binding interface of the

252 We suggest that MEKK1 is involved in a process of IB nucleation.

253 Our data suggest that MEKK1 transmits wound signals, leading to the transcript

254 n differentiation-defective, suggesting that MEKK1 does not contribute to the inhibitory actions of R

255 This study suggests that MEKK1-JNK signaling regulates Itch E3 ligase-mediated to

256 The MEKK1 PHD binds and mediates the transfer of Lys63-linke

257 The MEKK1 protein is a pivotal kinase activator of responses

258 The MEKK1 TOG domain binds to tubulin heterodimers-a canonic

259 he nuclear Lyn tyrosine kinase activates the MEKK1 --> MKK7 --> SAPK pathway but not through a direct

260 in tandem with Cdc42 and Rac1 activates the MEKK1/4, MEK1/MKK4, and JNK cascade, thereby stimulating

261 se results imply that thrombin activates the MEKK1/ERK/RSK1 signaling pathway, which in turn initiate

262 pathway is dependent on Smad activation, the MEKK1-mediated JNK and p38 activities are both essential

263 Both Itch and the MEKK1 kinase domain are important for Il4 and Il6 cytoki

264 e findings provide a direct link between the MEKK1 protein and tubulin, which is likely to be relevan

265 Both the MEKK1 PHD and TAB1 are critical for ES-cell differentiat

266 ivin B morphogenetic signals mediated by the MEKK1-MKK4 pathway.

267 We disrupted the MEKK1 kinase domain in chicken bursal B-cell line DT40 b

268 ion into mekk1 knockout plants of either the MEKK1 (K361M) construct or a nahG transgene that degrade

269 se results establish a specific role for the MEKK1-JNK cascade in transmission of TGF-beta and activi

270 cking MKK5 (MAPK kinase 5) activation in the MEKK1 (MAPK kinase kinase 1)/MEKKs-MKK4/5-MPK3/6 cascade

271 by mutation of the essential cysteine in the MEKK1 PHD domain.

272 tream kinases likely are not involved in the MEKK1-controlled transcriptional block.

273 tional component(s) upstream of MEKK1 in the MEKK1-MKK1/2-MPK4 cascade and the plasma membrane-locali

274 AF2-dependent manner, thereby initiating the MEKK1/MKK4-dependent activation of JNK activities.

275 Interestingly, the MEKK1-MKK2-MPK4 pathway constitutively suppresses MPK3 a

276 Interestingly in cells lacking the MEKK1 gene or expressing the dominant negative MEKK1, ER

277 lD3 is a dynamic junctional regulator of the MEKK1-c-Jun NH2-terminal kinase (JNK) pathway.

278 We examined the role of the MEKK1-JNK pathway in pressure-overloaded hearts by using

279 ap3k1(m) (PHD) ES cells demonstrate that the MEKK1 PHD controls p38 and JNK activation during TGF-bet

280 red cardiac myocytes have suggested that the MEKK1-JNK pathway plays a key role in hypertrophy and ap

281 MarvelD3 thus couples tight junctions to the MEKK1-JNK pathway to regulate cell behavior and survival

282 Thus, we propose a mechanism by which the MEKK1-dependent JNK/SAPK pathway is negatively regulated

283 Autophosphorylation within the MEKK1 kinase domain activation loop is required for acti

284 Therefore, MEKK1 regulates calpain-mediated substratum release of m

285 Thus MEKK1 controls tumor progression by regulating both the

286 Thus, MEKK1 appears to be required for pressure overload-induc

287 Thus, MEKK1 mediates cardiac hypertrophy induced by Galphaq in

288 Thus, MEKK1-induced apoptosis requires TRAIL death receptor ac

289 of RhoA but not of Rac and CDC42, leading to MEKK1-dependent phosphorylation of JNK and transcription

290 tion by RhoA and its overexpression leads to MEKK1 activation, we propose a RhoA-ROCK-MEKK1-JNK pathw

291 Moreover, binding of MKK4 to MEKK1 Delta protects the latter from cleavage at an engi

292 pendent down-regulation and are resistant to MEKK1-plus-R5020-induced transcriptional synergy but res

293 of this site inhibits binding of JNK/SAPK to MEKK1.

294 We demonstrate that growth factor-treated MEKK1-deficient fibroblasts display greatly reduced uPA

295 ng that Lyn activates PKCdelta, and in turn, MEKK1 is activated by a PKCdelta-dependent mechanism.

296 Conversely, expression of wild-type MEKK1 accelerates reepithelialization of full-thickness

297 lting from exogenous expression of wild-type MEKK1 and the opposite effect induced by expression of a

298 morphogenesis and that reduction of upstream MEKK1 signals uncovers analogous but differential roles

299 eta (ERbeta), which directly associates with MEKK1 to sequentially modulate MEK and ERK activation, w

300 s signaling cascade and forms a complex with MEKK1 and MLH1.

301 ay but not through a direct interaction with MEKK1.