ライフサイエンスコーパス: Tiam1

1 plexes to stimulate Rac activity via the GEF Tiam1.

2 lls and that it interacts with the 3'-UTR of Tiam1.

3 1 and its guanine nucleotide exchange factor Tiam1.

4 recruiting, phosphorylating, and activating Tiam1.

5 n, which in turn persistently phosphorylates Tiam1.

6 moter by Src were also potently increased by Tiam1.

7 the Rac1 guanine nucleotide exchange factor Tiam1.

8 naling through the G protein exchange factor Tiam1.

9 ive and require CD44s binding to the Rac GEF TIAM1.

10 RT1 or 2 has not been previously linked with TIAM1.

11 tion is required for the mitotic function of Tiam1.

12 and demonstrate that they act downstream of Tiam1.

13 nockdown resulted in enhanced acetylation of TIAM1.

14 protein-protein interaction between Rac1 and Tiam1.

15 junctional recruitment of the Rac1 activator Tiam1.

16 attenuated HGF-induced recruitment of c-Met, Tiam1 (a Rac1 exchange factor), cortactin (an actin cyto

17 f T-lymphoma invasion and metastasis gene 1 (Tiam1), a guanine nucleotide exchange factor.

18 f T-cell lymphoma invasion and metastasis 1 (TIAM1), a Rac guanine nucleotide exchange factor (GEF).

19 invasion and metastasis-inducing protein 1 (TIAM1)-a Rac guanine exchange factor-from the plasma mem

20 We present compelling evidence that TIAM1, a guanidine exchange factor of the Rac GTPase, is

21 lls, probably through microtubule-associated Tiam1, a guanine nucleotide exchange factor for Rac.

22 Tiam1, a newly identified guanine nucleotide exchange fa

23 ormation of a RAKEC consisting of CaMKII and Tiam1, a Rac-GEF.

24 d in diminished interaction between HRas and Tiam1, a Rac1-specific nucleotide exchange factor.

25 osomes during prophase and prometaphase, and Tiam1, acting through Rac, ordinarily retards centrosome

26 er, these findings suggest that HRG regulate Tiam1 activation and lymphoid enhancer factor/beta-caten

27 with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no effect on the deactivation o

28 Notably, mice lacking Tiam1 also exhibit enhanced contextual fear memory and c

29 brane translocation of the Rac1-specific GEF Tiam1 and activation of Rac1-dependent peripheral cytosk

30 acted in a protein complex with the Rac1 GEF TIAM1 and colocalized with actin at the platelet lamelli

31 promotes the plasma membrane localization of Tiam1 and enhances the ability of Tiam1 to activate p70

32 nduced localized Rac activation dependent on Tiam1 and IRSp53.

33 tor essential for centrosome separation, and Tiam1 and its substrate Rac antagonize Eg5-dependent cen

34 asal polarity is controlled by regulation of Tiam1 and Lis1.

35 haracterized mechanism for the activation of Tiam1 and of a role for this effector in neurotrophin-me

36 Here we show that Tiam1 and P-Rex1, two Rac GEFs, promote Rac1 anti- and p

37 the Rac1 guanine nucleotide exchange factor Tiam1 and phosphorylation of caveolin-1, indicative of s

38 We reveal that Tiam1 and Rac localize to centrosomes during prophase an

39 We demonstrate Tiam1 and Rac1 form a complex with RORgammat in the nucl

40 Tiam1 and Ras-GRF1 are guanine nucleotide exchange facto

41 These findings imply that Tiam1 and Ras-GRF1 can contribute to Rac signaling speci

42 We show that BAI1 interacts with Par3/Tiam1 and recruits these proteins to synaptic sites.

43 CEM fractions revealed complexes containing Tiam1 and S1P1.

44 nduced localized Rac activation dependent on Tiam1 and spinophilin.

45 decan1 is a physiological binding partner of Tiam1 and that the PDZ domain has a function in cell-mat

46 ates with NMDA receptors (NMDARs) along with Tiam1 and that this protein complex is more abundant in

47 l targets of the Wnt pathway, such as Mash2, Tiam1 and the Eph/Ephrins.

48 tudies suggest that the specificities of the Tiam1 and Tiam2 PDZ domains are distinct.

49 specific guanine nucleotide exchange factors Tiam1 and Trio (NSC23766).

50 Tiam1 and Trio siRNAs and dominant-negative Tiam1 were u

51 racts with and regulates the localization of Tiam1 and Trio, which are guanine nucleotide exchange fa

52 the Rac guanine nucleotide exchange factors Tiam1 and Vav1 in unstimulated peripheral blood CLL cell

53 a regulatory complex composed of a Rac-GEF (Tiam1) and a Rac-GAP (Bcr) that cooperate to control exc

54 otic (Raf, phosphatidylinositol 3-kinase and Tiam1) and apoptotic (Nore1 and RASSF1) actions of oncog

55 d invasive properties of cancer cells (e.g., TIAM1) and genes responsible for enhanced drug resistanc

56 ion of T lymphoma invasion and metastasis 1 (Tiam1) and its upstream activator Ras in a phosphoinosit

57 a and beta catalytic subunits, the Rac1 GEF, Tiam1, and alpha-actinin isoforms 1 and 4.

58 myloid beta (A4) precursor protein (APP) and TIAM1, and between immediate early gene (IEG) proteins a

59 show the guanine nucleotide exchange factor, Tiam1, and its cognate Rho-family G protein, Rac1, regul

60 Rac guanine nucleotide-exchange factor (GEF) TIAM1, and spatially restricting it to dendritic spines.

61 c were affected only in cells with exogenous Tiam1, and were primarily increased in the membrane frac

62 For example, Trio, GEF-H1, and Tiam1 are a subset of GEFs that specifically activate Ra

63 n levels in cancer cells, and DVL along with TIAM1 are known to augment Rac activation; however, SIRT

64 ssed Rac1 guanine nucleotide exchange factor Tiam1 are phosphorylated in tyrosine residues in cells t

65 Here, we identify TIAM1 as a critical antagonist of CRC progression throug

66 Here we identify S1466 of Tiam1 as a novel Cdk1 site whose phosphorylation is requ

67 In this study, we identified Tiam1 as a target of HRG signaling.

68 These findings establish Tiam1 as an essential regulator of DG granule cell devel

69 Here, we identify the Rac-GEF Tiam1 as an important regulator of DG development and as

70 n betagamma subunits, Src kinase and the GEF Tiam1 as upstream modulators of S1P-mediated Rac1 activa

71 inhibition (LY294002) attenuated S1P-induced Tiam1 association with S1P1, Tiam1/Rac1 activation, alph

72 ed and triggers the localized degradation of Tiam1 at AJs, likely involving calpain proteases.

73 TIAM1 attenuation, in turn, enhanced migration and invas

74 Notably, EphB receptors utilize the Tiam1-Bcr complex to control synaptogenesis.

75 Therefore, Tiam1 binding results in constitutive CaMKII activation,

76 e Tiam1-NMDAR interaction with a fragment of Tiam1 blocks OGD-induced Tiam1 activation but has no eff

77 GEF, DOCK2, but not by the Dbl homology GEF, TIAM1, both of which activate the parent protein.

78 h required the activity of Rac1 and its GEF, Tiam1, both of which show suppressed activity in the pre

79 blood CLL cells with almost complete loss of Tiam1 but increased transcription of the potential Rac a

80 to a subset of Rac GEFs, including VAV2 and Tiam1 but not others such as SWAP-70 or COOL-1.

81 Moreover, this compound reduced Trio or Tiam1 but not Vav, Lbc, Intersectin, or a constitutively

82 lamellipodia by the Rac-specific activator, Tiam1, but not by activated RhoG.

83 B, directly binds and specifically activates Tiam1 by phosphorylating Tyr-829, leading to Rac1 activa

84 Here we show that the N terminus of Tiam1 can influence Rac signaling specificity in a diffe

85 Tiam1 can then promote Rac1-dependent actin cytoskeletal

86 c release, followed by caspase-3 activation, Tiam1 cleavage, and a reduction in Rac1.GTP.

87 In spinophilin-deficient cells, Tiam1 co-localized with IRSp53 in response to pervanadat

88 In IRSp53-deficient cells, Tiam1 co-localized with spinophilin in response to forsk

89 However, the mechanisms that restrict Par-Tiam1 complex activity to the leading edge to maintain c

90 diated nucleotide exchange based on the Rac1-Tiam1 complex structure, with SopE/E2 flexibility, parti

91 te that Bcr is an integral member of the Par-Tiam1 complex that controls polarized cell migration by

92 rotein (Bcr) as a novel regulator of the Par-Tiam1 complex.

93 Further, the caspase-3-resistant TIAM1 construct C1199DN, a stable guanine exchange facto

94 Tiam1 contains multiple domains, including an N-terminal

95 t T-cell lymphoma invasion and metastasis 1 (TIAM1) contains a conserved EEVIWVRRE peptide that was a

96 We find that Tiam1 contributes to both of these processes by binding

97 mpling between the open and closed states of Tiam1 contributes to Rac1 dissociation.

98 e results demonstrate that overexpression of Tiam1 contributes to the metastatic phenotype of colon c

99 have shown previously that the N terminus of Tiam1 contributes to the signaling specificity of its do

100 at the SCF(betaTrCP)-mediated degradation of Tiam1 controls the duration of the mTOR-S6K signaling pa

101 Furthermore, Tiam1 cooperated with Src to induce activation of Rac1 i

102 nhibition of CK1 and MEK, or mutation of the Tiam1 degron site.

103 the guanine nucleotide exchange factor (GEF) Tiam1, dependent on its ability to activate the GTPase R

104 inally, IRSp53 depletion from cells prevents Tiam1-dependent lamellipodia induced by Tiam1 overexpres

105 Importantly, both Tiam1-depleted cells in culture and Rac1-deficient epith

106 Significantly, Eg5 suppression in Tiam1-depleted cells rectifies not only their increased

107 Moreover, Tiam1-depleted cells transit more slowly through prometa

108 expression of constitutively active Vav2 or Tiam1 derivatives.

109 Tiam1 directs IRSp53 to Rac signaling by enhancing IRSp5

110 trikingly, both male and female mice lacking Tiam1 exhibit enhanced contextual fear memory and contex

111 ng a close correlation between the status of Tiam1 expression and invasiveness of human breast tumor

112 ense oligonucleotide, that miR-10b represses Tiam1 expression in breast carcinoma cells and that it i

113 In marked contrast, reduced Tiam1 expression in CA1 pyramidal neurons produced no ef

114 tion (P = 0.019) was seen between miR-21 and TIAM1 expression in patients with hepatoma.

115 , correlations between TRalpha1, miR-21, and TIAM1 expression patterns in animal models paralleled th

116 Silencing of either S1P1 or Tiam1 expression resulted in the loss of S1P-mediated Ra

117 Here, Tiam1 expression was induced in the malignant cells in l

118 ell migration, and creates a docking site on Tiam1 for Grb2.

119 -inhibitory PH domain of Tiam1 in regulating Tiam1 function at these synapses.

120 We find that inhibition of Tiam1 function in dentate granule neurons reduces synapt

121 wn of Tiam1 protein by RNAi or inhibition of Tiam1 function with a dominant-negative Tiam1 mutant blo

122 Blockade of Tiam1 function with RNAi and dominant interfering mutant

123 for Rac1 GTP loading, whereas, surprisingly, Tiam1 functions as an adaptor in a VE-cadherin-p67phox-P

124 , we show that the PHn-CC-Ex domain inhibits Tiam1 GEF activity by directly interacting with the cata

125 ighlight the role of the PHn-CC-Ex domain in Tiam1 GEF regulation and suggest a combinatorial model f

126 Whereas Tiam1 genetic deficiency weakens IL-17A expression parti

127 vely, whereas LY294002 and dominant negative Tiam1 had no effect.

128 d activation by the Rac-specific GEF Trio or Tiam1 in a dose-dependent manner without interfering wit

129 Consistent with the involvement of Tiam1 in cell motility, we observed that miR-10b suppres

130 Moreover, phosphorylation of Tiam1 in cells treated with pervanadate, a potent inhibi

131 Importantly, high nuclear TIAM1 in clinical specimens associates with increased CR

132 Global deletion of Tiam1 in male mice results in DG granule cells with simp

133 al role for the auto-inhibitory PH domain of Tiam1 in regulating Tiam1 function at these synapses.

134 her, these data identify a critical role for Tiam1 in the hippocampus and reveal a unique Tiam1-media

135 and Rac-specific nucleotide exchange factor Tiam1 in the mechanisms of EC barrier protection by HGF.

136 To determine directly the role of Tiam1 in the migration of these migratory sublines, the

137 Ectopic expression of Tiam1 in these clones led to morphologic changes identic

138 thways in epithelial tumor cells and lack of Tiam1 in tumor cells retards tumor growth in Tiam1 knock

139 We have investigated the role of Tiam1 in tumor-associated fibroblasts as a modulator of

140 Following EphB activation, Tiam1 induces Rac1-dependent spine formation, whereas Bc

141 excessive synaptic growth that is rescued by Tiam1 inhibition.

142 Fibroblasts express at least two Tiam1-interacting proteins, insulin receptor substrate p

143 n activity led to the disruption of the DVL1-TIAM1 interaction.

144 We have shown that Tiam1 interactions with different scaffold proteins acti

145 These results support the idea that Tiam1 interactions with different scaffold proteins coup

146 the Rac1 guanine nucleotide exchange factor Tiam1 interacts with the EphB2 receptor in a kinase-depe

147 Tiam1 interacts with the NMDA receptor and is phosphoryl

148 the implantation of clones that overexpress Tiam1 into the cecum of athymic mice resulted in tumor g

149 Together, these results suggest that Tiam1 is a key regulator of DG granule cell stabilizatio

150 Tiam1 is a ubiquitous guanine nucleotide exchange factor

151 We find that Tiam1 is associated with ERK.

152 Enzyme kinetics experiments suggested that Tiam1 is auto-inhibited through occlusion of the catalyt

153 ere, we report that in response to mitogens, Tiam1 is degraded by the ubiquitin-proteasome system via

154 Thus, a balance of PAR-3 and TIAM1 is essential to modulate Rac-GTP levels and to all

155 The Rac exchange factor Tiam1 is implicated in multiple signaling pathways in ep

156 The Rac exchange factor Tiam1 is involved in diverse cell functions and signalin

157 ac1 provided by various extended portions of Tiam1 is not influenced by (a) soluble phosphoinositide

158 Here, we show that Tiam1 is phosphorylated on Y384 by Src.

159 In the hippocampus, Tiam1 is predominantly expressed in the DG throughout li

160 We report that the Rac1-GEF Tiam1 is present in dendrites and spines and is required

161 The proteolysis of Tiam1 is prevented by betaTrCP silencing, inhibition of

162 The Rac activator Tiam1 is required for adherens junction (AJ) maintenance

163 Indeed in LIM 1863 cells, suppression of TIAM1 is required for miR-21/miR-31 to enhance cell migr

164 We find that this phosphorylation of Tiam1 is required for the activation of group I p21-acti

165 TIAM1 is well known for its role in tumor metastasis, bu

166 T-cell lymphoma invasion and metastasis 1 (Tiam1) is a Dbl-family guanine nucleotide exchange facto

167 ell lymphoma invasion and metastasis gene 1 (Tiam1) is a guanine exchange factor (GEF) for the Rho-fa

168 Rac1 or Tiam1 knockdown using siRNA or treatment with the Tiam1/

169 Moreover, Tiam1 knockdown using the siRNA approach, attenuated the

170 Conversely, tumors arising in Tiam1 knockout mice have increased invasiveness.

171 Tiam1 in tumor cells retards tumor growth in Tiam1 knockout mouse models.

172 l dendrites and synapses develop normally in Tiam1 KO mice, resembling WT mice at postnatal day 21 (P

173 r, based on the enhanced memory phenotype of Tiam1 KO mice, Tiam1 may be a potential target for the t

174 Furthermore, loss of Tiam1 led to the disruption of redox signaling both in v

175 vely correlates with Src activity, and total Tiam1 levels are inversely correlated.

176 al delivery of short hairpin RNA to suppress Tiam1 levels in three different experimental models.

177 In the cytoplasm, TIAM1 localizes to the destruction complex and promotes

178 Tiam1 loss also increases the survival, but not the prod

179 ac1 guanine nucleotide exchange factor (GEF) Tiam1 markedly enhanced Rac1 activity, whereas a dominan

180 ogether, these results suggest that Vav2 and Tiam1 may act as downstream effectors of Src, thereby re

181 utes to the progression of melanoma and that Tiam1 may activate Rac in nodular presentations.

182 enhanced memory phenotype of Tiam1 KO mice, Tiam1 may be a potential target for the treatment of dis

183 These results suggest that stromal Tiam1 may have a role in modulating the effects of the t

184 Tiam1 in the hippocampus and reveal a unique Tiam1-mediated molecular program of glutamatergic synaps

185 ta provide a mechanism for the regulation of Tiam1-mediated Rac activation in breast cancer cells and

186 y, we demonstrate that miR-10b also inhibits Tiam1-mediated Rac activation.

187 The Rac1 guanine nucleotide exchange factor Tiam1 mediates an OGD-induced increase in Rac1 activity

188 t interfering mutants of Tiam1 suggests that Tiam1 mediates effects of the NMDA receptor on dendritic

189 BAI1 knockdown results in Par3/Tiam1 mislocalization and loss of activated Rac1 and fil

190 n of Tiam1 function with a dominant-negative Tiam1 mutant blocks dendritic spine formation induced by

191 d Rac1 activity, whereas a dominant negative Tiam1 mutant significantly attenuated S1P-mediated Rac1

192 Expression of a stable Tiam1 mutant that is unable to interact with betaTrCP re

193 Furthermore, disrupting the Tiam1-NMDAR interaction with a fragment of Tiam1 blocks

194 These findings indicate that Tiam1 not only activates Rac but also contributes to Rac

195 In addition, silencing Tiam1 or dynamin 2 reduced HGF-induced Rac1 activation,

196 Furthermore, ectopic expression of Tiam1 or of an active beta-catenin mutant led to potenti

197 In addition, Tiam1 or Ras-GRF1 binding to IB2/JIP2 increases the asso

198 IB2/JIP2 in cells potentiates the ability of Tiam1 or Ras-GRF1 to activate the p38 MAP kinase cascade

199 ll as Rac-dependent transformation caused by Tiam1 or Ras.

200 Finally, silencing S1P1, Tiam1, or both alpha-actinin isoforms 1/4 inhibits S1P-i

201 -stimulated cell growth and suppressed Trio, Tiam1, or Ras-induced cell transformation.

202 Stimulation of endogenous Rac-1 by Tiam1 overexpression elicited a similar hormone-independ

203 ents Tiam1-dependent lamellipodia induced by Tiam1 overexpression or platelet-derived growth factor s

204 data report on a physiological role for the Tiam1 PDZ domain and establish a novel link between two

205 proteins, Syndecan1 and Caspr4, as potential Tiam1 PDZ domain binding proteins.

206 We determined the crystal structures of the Tiam1 PDZ domain free and in complex with a "model" pept

207 Remarkably, a Tiam1 PDZ domain quadruple mutant had the same specifici

208 two regions (S(0) and S(-2) pockets) of the Tiam1 PDZ domain that are important determinants of liga

209 synthetic peptide capable of binding to the Tiam1 PDZ domain, but little is known about its ligand s

210 structure, specificity, and function of the Tiam1 PDZ domain.

211 structure, specificity, and function of the Tiam1 PDZ domain.

212 derived from Syndecan1 and Caspr4 bound the Tiam1 PDZ domain.

213 ur residues important for specificity in the Tiam1 PDZ into the Tiam2 PDZ domain, as a model system t

214 of the Tiam2 QM was switched to that of the Tiam1 PDZ.

215 perturbation experiments indicated that the Tiam1 PDZ/Syndecan1 and PDZ/Caspr4 complexes were struct

216 Thus, our data implicate Tiam1 phosphorylation and consequent degradation in Src-

217 We find that Tiam1 plays a critical role in the development of glutam

218 guanine-nucleotide exchange factor) protein Tiam1 plays a unique role in the regulation of glutamate

219 interaction between the small GTPase Ras and Tiam1 plays an essential role in the activation of Rac1.

220 Osteopontin-CD44s-TIAM1 promotes clonal growth in vitro but not at high ce

221 These results indicate that Tiam1 promotes DG granule cell dendrite and synapse stab

222 Moreover, Tiam1 promotes IRSp53 localization to Rac-induced lamell

223 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal re

224 Phosphorylated Tiam1 promotes stable actin-polymerization through Rac1,

225 cking the Rac-GEF Tiam1, we demonstrate that Tiam1 promotes the stabilization of DG granule cell dend

226 Either knockdown of Tiam1 protein by RNAi or inhibition of Tiam1 function wi

227 was transfected with a plasmid encoding the Tiam1 protein, and single cell clones were established.

228 ting both guanine nucleotide association and Tiam1 Rac guanine nucleotide exchange factor-stimulated

229 These findings identify Tiam1-Rac signaling as the first antagonist of centrosom

230 st that mutant B-RAF signaling downregulates Tiam1/Rac activity resulting in an increase in N-cadheri

231 st that mutant B-RAF signaling downregulates Tiam1/Rac activity resulting in an increase in N-cadheri

232 n where SIRT1/2 positively modulates the DVL/TIAM1/Rac axis and promotes sustained pathway activation

233 knockdown using siRNA or treatment with the Tiam1/Rac inhibitor NSC-23766 attenuated c-Myc transcrip

234 This study demonstrates the Tiam1/Rac-dependent mechanism of HGF-induced EC barrier

235 ty via dynamic interactions between Rho- and Tiam1/Rac-mediated pathways.

236 ent, a process with essential involvement of Tiam1, Rac1, dynamin 2, and cortactin.

237 These data identify osteopontin-CD44-TIAM1-Rac1 axis as a RhoGDI2-sensitive pathway and poten

238 gents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of

239 al permeability requires the activation of a Tiam1-Rac1 signaling module, suggesting a novel therapeu

240 In the same time frame with Tiam1-Rac1 translocation, the junctional proteins ZO-1 a

241 inhibits cell migration by blocking the Ras-Tiam1-Rac1-Pak1 signaling pathway in endothelial cells.

242 omains in the related structures of Sos1 and Tiam1.Rac1.

243 o CEM fractions promotes PI3 kinase-mediated Tiam1/Rac1 activation required for alpha-actinin-1/4-reg

244 ted S1P-induced Tiam1 association with S1P1, Tiam1/Rac1 activation, alpha-actinin-1/4 recruitment, an

245 on through two parallel signaling units, Ras/Tiam1/Rac1 and Dbs/Cdc42, and that Schwann cell migratio

246 r findings highlight a regulatory pathway of Tiam1/Rac1 in Th17 cells and suggest that it may be a th

247 defects by activating a calcium/CamKinaseII/Tiam1/Rac1 pathway that substitutes for fibronectin-depe

248 receptor expression blocked OxPAPC-mediated Tiam1 recruitment to CEMs, Rac1 activation, and EC barri

249 The exchange factor Tiam1 regulates multiple cellular functions by activatin

250 Further, overexpression of Tiam1 rescues BAI1 knockdown spine phenotypes.

251 reas a mutant that cannot interact with Par3/Tiam1 rescues neither spine defects nor Par3 localizatio

252 1 induced upregulation and downregulation of TIAM1, respectively.

253 , simultaneous depletion of B-RAF and Rac or Tiam1 resulted in invasive capacity similar to that of c

254 We also find that Tiam1's support of perforant path-DG synapse function is

255 ream pathways, and suggest that manipulating Tiam1-scaffold interactions can modulate Rac-dependent c

256 veral multiphosphorylated phosphoinositides, Tiam1 selectively interacts with phosphatidylinositol 3-

257 t Dbl family proteins, intersectin, Dbs, and Tiam1, selectively bind lipid vesicles only when phospho

258 We demonstrate that TIAM1 shuttles between the cytoplasm and nucleus antagon

259 RNA (siRNA) based depletion of either Rac or Tiam1 significantly attenuated HGF-induced peripheral tr

260 vasion and metastasis, which was reversed by Tiam1 silencing in co-injected fibroblasts.

261 In tissue-engineered human skin, Tiam1 silencing in dermal fibroblasts led to increased i

262 of mammary epithelial cells and fibroblasts, Tiam1 silencing in fibroblasts led to increased epitheli

263 Overexpressed VAV2 and Tiam1 specifically require Rap1 to promote spreading, ev

264 inase activation in cells, suggesting that a Tiam1/spinophilin complex contributes to p70 S6 kinase r

265 us studies indicate that larger fragments of Tiam1, such as the region encompassing the N-terminal to

266 ith RNAi and dominant interfering mutants of Tiam1 suggests that Tiam1 mediates effects of the NMDA r

267 ly, a mutant spinophilin that cannot bind to Tiam1 suppresses serum-induced p70 S6 kinase activation

268 Nuclear TIAM1 suppresses TAZ/YAP interaction with TEADs, inhibit

269 Together, our findings suggest that in CRC TIAM1 suppresses tumor progression by regulating YAP/TAZ

270 at miR-21 stimulation by T(3) and subsequent TIAM1 suppression promotes hepatoma cell migration and i

271 ysis of potential miR-10b targets identified Tiam1 (T lymphoma invasion and metastasis 1), a guanidin

272 specific guanine nucleotide exchange factor, Tiam1 (T lymphoma invasion and metastasis 1), in transdu

273 Tiam1 (T-cell lymphoma invasion and metastasis 1) is a g

274 cal analysis revealed that the Rac activator Tiam1 (T-cell lymphoma invasion and metastasis 1) is ove

275 t2 (epithelial cell transforming squence 2), Tiam1 (T-cell lymphoma invasion and metastasis 1), Vav a

276 With the exception of Tiam1, target gene expression generally showed no differ

277 ization of Tiam1 and enhances the ability of Tiam1 to activate p70 S6 kinase.

278 hus, Par3 coordinates the action of PI3K and Tiam1 to define membrane identity, revealing a signaling

279 tyrosine phosphorylation and recruitment of Tiam1 to EphB complexes containing NMDA-type glutamate r

280 the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes syna

281 , and that simultaneously targeting PI3K and Tiam1 to the apical membrane has a synergistic effect on

282 itogenic stimulation triggers the binding of Tiam1 to the F-box protein betaTrCP via its degron seque

283 Accumulation of PA and binding of TIAM1 to the membrane require the activity of phosphatid

284 ed the phosphorylation and redistribution of Tiam1 to the membrane ruffles and the loosening of inter

285 vely active PI3K stimulated translocation of Tiam1 to the membrane, increased Rac1 activity, and incr

286 factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promot

287 cell adhesion or migration, including SS18, TIAM1, TSTA3 and LDB2, which warrant further investigati

288 A point mutation in Tiam1, Tyr-829 to Phe-829, blocked these BDNF-induced ch

289 aTrCP via its degron sequence and subsequent Tiam1 ubiquitylation and proteasomal degradation.

290 Overexpression of the GEF Tiam1 unexpectedly decreased k(off) for wtRac, most like

291 Tiam1 was required for the activation of Rac1, actin pol

292 , T-cell lymphoma invasion and metastasis 1 (TIAM1), was identified as a miR-21 target additionally d

293 Using truncated mutants of Tiam1, we demonstrate that multiple sites can be tyrosin

294 By characterizing mice lacking the Rac-GEF Tiam1, we demonstrate that Tiam1 promotes the stabilizat

295 1 and its guanine nucleotide exchange factor Tiam1 were found associated with a membrane fraction fro

296 Tiam1 and Trio siRNAs and dominant-negative Tiam1 were used to determine which Rac1-specific guanine

297 d SIRT2 resulted in increased acetylation of TIAM1, whereas chronic SIRT2 knockdown resulted in enhan

298 are known to phosphorylate the Rac activator Tiam1, which has recently been shown to be Abeta-respons

299 ediated by a pseudo-autoinhibitory domain on Tiam1, which is homologous to the CaMKII autoinhibitory

300 naptic regulatory role of the RhoGEF protein Tiam1, whose expression appears to be remarkably enriche