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 expression increased progestin-mediated transcript

9 MEKK1 expression resulted in phosphorylation of PR on Se

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

11 MEKK1 induced AR-dependent apoptosis in prostate cancer

12 MEKK1 inhibits MyoD-directed transcriptional activity wi

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

14 MEKK1 is a MAPKKK that regulates both the extracellular

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

16 MEKK1 is a mitogen-activated protein kinase kinase kinas

17 MEKK1 is a strong activator of p42 and p44 MAPKs.

18 MEKK1 is activated in response to growth factors and cyt

19 MEKK1 is associated with actin fibers and focal adhesion

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

21 MEKK1 is required for activation of the cysteine proteas

22 MEKK1 kinase activity is required for ubiquitylation of

23 MEKK1 may play a structural role in signaling, independe

24 MEKK1 phosphorylates and activates MKK1 and MKK4, leadin

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

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

27 MEKK1 signaling regulates migration through control of c

28 MEKK1 strongly stimulated recruitment of polyQ polypepti

29 MEKK1 ubiquitylation is inhibited by mutation of cystein

30 MEKK1 ubiquitylation represents a mechanism for inhibiti

31 MEKK1 was recruited to CD40 and adaptor molecule TRAF2 a

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

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

34 MEKK1-deficient mice with mammary gland-targeted express

35 MEKK1-dependent signaling regulates HECT E3 ligase Itch,

36 MEKK1-driven JNK activation is required for actin stress

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

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

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

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

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

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

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

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

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

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

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

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

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

50 Constitutive active forms of c-Raf-1, MEKK1 and MKK6, proximal regulators of the ERKs, JNKs, a

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

52 ction of AP-1 reporter gene by active Raf-1, MEKK1, or MKK6, suggesting that it inhibited MAPK pathwa

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

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

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

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

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

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

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

60 that purified, active GCK and TRAF2 activate MEKK1.

61 itor SP600125 and was repressed by activated MEKK1.

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

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

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

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

66 -9-dependent cleavage of c-Jun at Asp-65 and MEKK1-mediated ubiquitylation and degradation of c-Jun i

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

68 strogen receptor activation by estrogens and MEKK1.

69 transcriptional activation by estrogens and MEKK1.

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

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

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

73 erminal kinase 1 activity, MEK1,2, MKK4, and MEKK1 were constitutively activated in clones stably tra

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

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

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

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

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

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

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

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

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

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

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

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

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

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

88 asis for the regulation of eyelid closure by MEKK1.

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

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

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

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

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

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

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

96 increase in ERK activation was inhibited by MEKK1 siRNA.

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

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

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

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

101 4 but does not appear to be ubiquitinated by MEKK1 under conditions that result in modification of ER

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

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

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

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

106 cits enhanced oligomerization of coexpressed MEKK1 in vivo.

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

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

109 Delayed MEKK1-dependent tumor dissemination is associated with m

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

129 overloaded hearts by using mice deficient in MEKK1.

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

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

132 2 activation and chemotaxis are inhibited in MEKK1-/- fibroblasts.

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

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

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

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

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

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

139 rmation with a construct carrying the intact MEKK1 gene.

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

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

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

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

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

145 ation is dependent on the MAPK kinase kinase MEKK1.

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

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

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

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

150 Activation of JNK by either upstream kinase MEKK1 or DLK or by expression of Wnt signaling proteins

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

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

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

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

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

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

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

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

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

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

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

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

163 of PKG were inhibited by a dominant negative MEKK1.

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

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

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

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

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

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

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

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

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 The deficiency of MEKK1 blocked posttranslational downregulation of c-Jun

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

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

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

187 Pases interact with the regulatory domain of MEKK1.

188 ctly phosphorylated the N-terminal domain of MEKK1.

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

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

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

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

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

194 We demonstrate that the active form of MEKK1, a protein kinase that regulates several stress-ac

195 Dominant negative forms of MEKK1 and MEKK4 were expressed stably in the clones harb

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

197 impinge upon the regulation and function of MEKK1.

198 orylated and activated NHE1 independently of MEKK1.

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

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

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

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

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

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

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

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

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

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

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

210 e activity is required for ubiquitylation of MEKK1.

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

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

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

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

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

216 n of uPA expression is strongly dependent on MEKK1.

217 the signaling molecules upstream of Raf-1 or MEKK1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

232 dicates that the EGCG response requires Ras, MEKK1, MEK3, and p38 kinases.

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

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

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

236 Previous studies suggest that a PKC/Ras/MEKK1 cascade regulates involucrin (hINV) gene expressio

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

284 Thus MEKK1 controls tumor progression by regulating both the

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

286 Thus, MEKK1 mediates cardiac hypertrophy induced by Galphaq in

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

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

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

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

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

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

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

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

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

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

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

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

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

300 ay but not through a direct interaction with MEKK1.