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"Tiam1 mediated Rac activation was dependent on PI3-kinase activity both on a collagen I and fibronectin substrate, suggesting that PI3-kinase is required for Tiam1 and Rac induced cell migration as well as E-cadherin- mediated cell-cell adhesion."
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"Based on these data, Zheng and coworkers concluded that NSC23766 represents a specific inhibitor of Tiam1 mediated activation of Rac1 [XREF_BIBR, XREF_BIBR]."
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"One study implicated Tiam1 mediated Rac activation in neuronal cell polarization, whereas another study reported that a Par3 mediated inactivation of Tiam1 and Rac is required for the polarization of epithelial MDCK cells."
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"The Rac activator Tiam1 and Ras induced oncogenesis."
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"Tiam1 and P-Rex1 induce differential Rac1 downstream effects."
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"Reduction in expression of either SIP 1 or Tiam1 (via siRNA techniques) or inhibition of PI3 kinase by LY294002 inhibits S1P induced Rac1 activation, cortical actin rearrangement and endothelial barrier enhancement."
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"Transient PDGF induced as well as sustained Rac activation by Tiam1 or V12Rac downregulate Rho activity."
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"TIAM1 activates Rac1 and stimulates neuronal migration by regulating actin cytoskeleton dynamics, and JNK regulates microtubule dynamics by stimulating MAP1B phosphorylation to control neuronal migration[ xref ]."
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"Our studies identify the Rac activator Tiam1 as a critical regulator of different aspects of Ras induced tumour formation."
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"Membrane trafficking between compartments has also been suggested, for example, activation of Rac by Tiam1 on endosomes resulted in protrusive activity on the plasma membrane and cell migration. xref "
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"To analyze the functional relevance of Tiam1 and Rac1 physical interaction with RORgammat in Th17 cells, we investigated the ability of Tiam1 mediated Rac1 activation to induce the Il17 promoter in reporter assays using 293T cells."
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"Adherens junction maintenance requires the Rac activator Tiam1."
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"Through our work, we confirm that Tiam1 activation of Rac1 stimulates cell–cell adhesion and reduces cell migration."
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"Transient PDGF-induced as well as sustained Rac activation by Tiam1 or V12Rac downregulate Rho activity."
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"The guanine nucleotide exchange factor, Tiam1, specifically activates the Rho-like GTPase Rac ( xref ) and Tiam1-Rac signaling affects cell migration ( xref ; xref ), invasion ( xref ; xref ; xref ), and metastasis ( xref ) of tumour cells."
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"Oncogenic RAS stimulates MP by engaging TIAM1, which activates RAC1 and thereby enhances PM ruffling."
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"The RhoA effector ROCK phosphorylates Par3, thereby inducing disruption of the Par complex, deregulation of Rac activator Tiam1 and impaired Rac activation [XREF_BIBR]."
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"Through computational screening of the surface of Rac1 known to interact with GEFs, the small molecule NSC23766 was discovered, which inhibited activation of Rac1 by the Rac-specific GEFs Trio and Tiam1, but not GEF activation of RhoA or Cdc42 in vitro and in cells xref ."
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"However, a possible role for this C-PH domain is to promote protein protein contacts with Tiam1 ligands that stimulate Rac1 activity."
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"The Rac activator Tiam1 is required for alpha3beta1 mediated laminin-5 deposition, cell spreading, and cell migration."
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"GTP is dispensable for Rac1 activation by constitutively active VAV2 and Tiam1, but do not exclude the possibility that Rap1 regulates to the catalytic activity of full-length GEFs in physiological conditions."
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"Together, these data indicate that upon the formation of PAs, Tiam1 mediated Rac activation is required for activation of the polarity complex, leading to TJ maturation."
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"Therefore, we determined in more detail the effect of Tiam1 mediated Rac activation on the activity state of endogenous Rho protein."
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"The PI3-kinase-dependent Rac activation by Tiam1, and the subsequent decrease in cell-cell adhesion upon inhibition of PI3-kinase activity, also suggests a role for PI3-kinase in the establishment of E-cadherin-mediated cell-cell adhesion."
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"Many PAR-mediated processes require activation of the GTPase Rac1 by Tiam1, a Rac-specific guanine nucleotide exchange factor (GEF) ( xref )."
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"In fibroblasts, however, Tiam1 mediated activation of Rac is associated with an increase in cell-cell interactions and loss of cell motility."
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"Together, these data demonstrate that pharmacological inhibition of Tiam1 mediated activation of Rac1 results in inhibition of GSIS in normal rat islets and clonal beta-cells."
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"Thus, GLS2 blocked the binding of Tiam1 and VAV1 to Rac1-GDP, and inhibited the Rac1 activation by Tiam1 and VAV1."
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"In this study, we show that Tiam1 mediated Rac activation controls TJ biogenesis and cell polarity by association with and activation of the Par polarity complex in keratinocytes."
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"So we propose that the dynamics of junction assembly and TER development result at least in part from a balance between Tiam1 mediated Rac1 activation and MgcRacGAP mediated Rac1 inhibition."
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"TIAM1 activates the Rac subfamily of Rho GTPases and its expression is associated with lymph node metastasis in lung adenocarcinoma ( xref )."
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"When overexpressed, nm23H1 co-immunoprecipitated with Tiam1, decreased the amount of Tiam1 that translocated to the membrane as cells were plated on fibronectin, and inhibited Tiam1-induced Rac1 activation and motility."
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"We showed that LC1 is sufficient to promote Tiam1-dependent Rac1 activation."
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"It was previously demonstrated that Tiam1 can activate Rac1 and Cdc42 in in vitro exchange assays, and Rac1 in cell based assays [XREF_BIBR]."
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"Therefore it is likely that moverastin might inhibit cell migration not only by inhibiting protein farnesylation, but also by inhibiting Tiam1 mediated Rac1 activation."
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"In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1."
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"Forskolin or epinephrine induced localized Rac activation dependent on Tiam1 and spinophilin."
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"Transfection of dominant-negative N17 Cdc42 did not affect the Tiam1 phenotype (Fig. xref C ), consistent with Tiam1 activating Rac rather than Cdc42."
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"A further MALDI-TOF study targeted T Lymphoma invasion and metastasis 1 (Tiam 1), a guanine nucleotide exchange factor that activates Rac (a GTPase responsible for stimulating cell spreading and migration)."
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"Finally, we have shown that Rac signaling is critical for force generation when Rac is activated by Vav1 but not when Rac is activated by Tiam1; these results illustrate the complexity of signaling that occurs upstream of force generation."
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"One of the logical candidates would be the guanine nucleotide exchange factor, Tiam-1, which was shown to specifically activate Rac1, but not Cdc42 (Sander et al. 1999)."
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"Since M S C580 Tiam1, but not C580 Tiam1, induces membrane ruffling, it is unlikely that the activation of cytoplasmic Rac by Tiam1 leads to the membrane translocation of GTPbound Rac."
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"XREF_BIBR, XREF_BIBR For example, Ras binds to and activates T-lymphoma invasion and metastasis inducing protein 1 (TIAM1), a GEF for Rac1 that may activate Rac1 to contribute to Ras transformation."
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"Bcr therefore serves to restrict Tiam1 induced Rac1 activation to an optimal range that promotes excitatory synapse formation and growth while preventing receptor endocytosis and synapse loss."
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"To further investigate the mechanistic details underlying Tiam1 mediated Rac1 activation by NGF, we analyzed whether H-Ras was required for both Tiam1-Rac1 interaction and Rac1 activity in response to NGF."
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"The signaling mechanism involved recruitment of sphingosine 1-phosphate receptor-1 (S1P-R1) to the caveolin enriched microdomains (CEMs, also known as lipid rafts or caveoli) and activation of serine/threonine kinases mammalian target of rapamycin (mTOR) and phosphoinositide 3-kinase (PI3K) and Rac specific nucleotide exchange factors Tiam1 and Vav2, which stimulated Rac1 GTPase signaling to cytoskeleton and cell junctions."
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"Together these results suggest that Tiam1 activation of Rac1 is associated with reduced cell migration potentially through its ability to increase actin and cadherin deposition at cell–cell contacts, as previously suggested xref xref ."
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"Down-regulation of Par3 in MDCK cells, as studied by XREF_BIBR, might prevent the recruitment of Tiam1 to cell-cell contacts and, thereby, promote Tiam1 mediated Rac activation at the cell periphery, leading to the destabilization of cell-cell adhesions and the inhibition of TJ formation."
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"Secondly, it has been shown that Tiam1-induced Rac1 activation promotes E-cadherin-mediated cell–cell adhesion in MDCKII and MDCK-f3 cells, it promotes N- and P-cadherin-mediated cell–cell adhesion in[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"Synaptic activity activates various Rac modulators, such as Tiam1, Kalirin-7, and betaPIX, and enhances the formation of dendritic spines through the activation of the Rac signaling pathway."
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"The activation of Rac1 by Tiam-1 was described to be associated with tumor progression in T cell lymphoma [19] , and Rac1 was also reported to inhibit apoptosis in the human lymphoma cells through th[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"For example in the Rho subfamily, Tiam1 is a specific activator of Rac1 while Vav promiscuously bind RhoA, RhoG, Rac1, and Cdc42."
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"BDNF-stimulated neuronal morphogenesis is known to require Rac1 activation by Tiam1 ( xref ; xref )."
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"The Rac1-GEFs, Tiam1 and Tiam2, directly interact with Par3 to induce the formation of the Par cell polarity complex [XREF_BIBR], activate Rac1, and promote the formation of neurite outgrowths in N1E-115 cells [XREF_BIBR, XREF_BIBR, XREF_BIBR]."
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"XREF_BIBR Additionally, Tiam1 mediated activation of Rac1 is also associated with reduced HGF- and epidermal growth factor (EGF)-induced cell scattering, further demonstrating the importance of Tiam1-Rac1 signaling in stabilizing cell-cell contacts."
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"The above findings have immediate relevance to our current findings for potential involvement of Tiam1 mediated Rac1 activation in GSIS."
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"XREF_BIBR In this model, loss of Par3 activates the GTPase Rac1 by delocalizing the Rac activator Tiam1, XREF_BIBR and Tiam1 itself is necessary for ErbB2 mediated mammary tumor growth and metastasis (XREF_FIG)."
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"Rac activation by Tiam1 requires PI3-kinase activity."
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"These results suggest that Tiam1 mediates the stimulatory effects of Rac1 on canonical Wnt signalling, and this is supported by the reduction in beta-catenin and TCF-dependent transcription in response to Tiam1 knock-down."
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"Tiam1, a Rac1 guanine nucleotide exchange factor, is phosphorylated by EphBs and promotes Rac1 dependent actin cytoskeletal remodeling for dendritic spine morphogenesis."
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"The Tiam1 mediated Rac activation regulates the further production, secretion, and organized deposition of LN5, which is essential for the spreading and migration of keratinocytes."
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"Recent work has established that Tiam1 can activate Rac downstream of LFA-1 in T cells ( xref ), although it remains unclear whether PIP 3 is involved."
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"Activation of Rac by Tiam1 induces an epithelial like morphology with functional cadherin based adhesions and inhibits migration of fibroblasts."
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"These results suggest that Tiam1 mediated Rac activity is required for full activation of Pak1/2 on centrosomes in prophase, and that this change in Pak activity does not influence Aurora A activation."
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"While Tiam1 appear to mediate NT-3 and BDNF-induced Rac1 activation, it is not clear whether activation of Rac1 by Tiam1 is critical for biological responses induced by NGF and TrkA."
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"TIAM1 activates Rac1 by catalyzing the exchange of inactive guanosine 5′-diphosphate–bound Rac for active GTP-bound Rac, which in turn activates downstream pathways that can lead to increased migratio[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"These studies indicate that the Rac activator Tiam1 is essential for the formation as well as the maintenance of cadherin based adhesions."
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"The Rac1 activator Tiam1 is inhibited by internal interactions."
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"NSC23766, a specific inhibitor of Tiam1 mediated activation of Rac1, markedly attenuated glucose induced, but not KCl induced insulin secretion in INS 832/13 cells and normal rat islets."
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"These results demonstrate that Tiam1 induced activation of Rac prevents Rho dependent neurite retraction and cell rounding."
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"Activation of Tiam1 most likely involves binding to lipid products of PI3-kinase, since Tiam1 mediated Rac activation is dependent on PI3-kinase activity."
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"Further, using in vitro experimental approaches, these researchers have also demonstrated specific inhibition of Tiam1 mediated activation of Rac1 by NSC23766, without significantly affecting the activation of Cdc42 or Rho by their respective GEFs [XREF_BIBR, XREF_BIBR]."
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"We previously showed that Tiam1 induced Rac activation promotes E-cadherin-mediated cell-cell adhesion in epithelial cells (Hordijk et al. 1997; Sander et al. 1998)."
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"The Rac activator Tiam1 controls tight junction biogenesis in keratinocytes through binding to and activation of the Par polarity complex."
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"As Pak1/2 are direct effectors of Rac1, we hypothesized that Tiam1-dependent Pak1/2 centrosomal activation was due to Tiam1 activation of Rac1."
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"To confirm that the increase in LN5 mRNA levels was because of Tiam1 mediated Rac activation, we analyzed Tiam1-/- keratinocytes that were reconstituted with Tiam1 and constitutive active V12Rac1 (XREF_FIG)."
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"Tiam1 can then promote Rac1 dependent actin cytoskeletal remodeling required for dendritic spine morphogenesis."
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"Tiam1 mediated Rac activation is required for Rap1 induced polarization of T cells."
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"Our results indicate that the Rac activator Tiam1 controls the intracellular redox balance by Nox mediated ROS production, which regulates ERK phosphorylation and the susceptibility of keratinocytes to apoptotic signaling."
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"As Pak1/2 are direct effectors of Rac1, we hypothesized that Tiam1 dependent Pak1/2 centrosomal activation was due to Tiam1 activation of Rac1."
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"However, and consistent with recent studies, we find that the formation of the signaling complex Tiam1 and Rac1 is not abrogated by inhibition of PI3K using Ly294002, indicating that Tiam1 mediates Rac1 activation by a PI3K independent mechanism XREF_BIBR, XREF_BIBR (XREF_SUPPLEMENTARY)."
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"Based on these data, these researchers have concluded that Tiam1 mediated activation of Rac1 is necessary for LPA 's effects in these cells."
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"Furthermore, Tiam1 cooperated with Src to induce activation of Rac1 in vivo and the formation of membrane ruffles."
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"77 HGF protects against thrombin induced EC dysfunction by Tiam1 mediated activation of Rac and inhibition of Rho pathways."
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"In support of this notion, Tiam1, Vav2 and Asef, Rac GEFs that contain a PIP3 binding PH domain, have been shown to activate Rac1 in response to EGF XREF_BIBR XREF_BIBR."
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"Rac activation by Tiam1, however, leads to signaling events that are not necessary for macrophage force generation."
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"As stated above, NSC23766 has been used to specifically inhibit Tiam1 mediated activation of Rac1 in multiple cell types."
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"Tiam1 can activate Rac1, but not Cdc42 [ xref , xref ] and it is involved in T cell trafficking [ xref ]."
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"XREF_BIBR Interestingly, in a recent proteomic study, both Tiam1 and Rac1 were shown to interact with IQGAP1, XREF_BIBR further supporting the notion that Tiam1 modulates the Rac1 interactome via its scaffolding function."
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"Taken together, it is evident that GSIS involves transient activation of Rac1, which is mediated by Tiam1 and Vav2."
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"Silencing Tiam1 impaired both ephrinA1 dependent activation of Rac1 and EphA2 endocytosis, definitely establishing Tiam1 as an important modulator of EphA2 signalling."
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"This suggests that actin accumulation in lamellae as well as in adherens junctions is linked to PI3-kinase-induced, Tiam1 mediated Rac activation."
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"MAP1B is found to interact with Tiam1 thereby activating Rac1 and cdc42 and further inhibiting RhoA activity which leads to actin polymerization and axonal elongation XREF_BIBR, XREF_BIBR."
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"Rac activation by Tiam1 requires PI3-kinase activity on all substrates."
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"Thus, our data suggest that Rac contributes to the progression of melanoma and that Tiam1 may activate Rac in nodular presentations."
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"These findings indicate that Tiam1 not only activates Rac but also contributes to Rac signaling specificity through binding to IRSp53."
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"TIAM1 activates the Rac subfamily of Rho GTPases and its expression is associated with lymph node metastasis in lung adenocarcinoma."
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"In addition, Tiam1-activated Rac1 stimulates the novel family of serine/threonine kinases, p-21 activated kinases ( xref ; xref ; xref ), which mediates actin assembly and induce the formation of membrane ruffling and lamellipodia (membrane projections)."
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"dbcAMP induced Rac1 activation was principally mediated by protein kinase A (PKA) and Sif- and Tiam1 like exchange factor (STEF)/Tiam2."
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"Expression of V12Rac1 produced a phenotype very similar to that of Tiam1, which is consistent with earlier observations that Tiam1 activates Rac1."
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"Tiam1 localization at the PM should activate Rac and its downstream signaling circuits that lead to formation of ruffling and lamellipodia."
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"Since the EHop-016 inhibitor was developed to block the association of Vav1 with Rac1 and, to a lesser extent, the activation of Rac1 by Tiam1, we wanted to determine if either of these GEFs was invol[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"Activation of Rac1 by the exchange factor TIAM1 or DOCK7 promotes axon formation in part by changing the activity of the microtubule severing protein stathmin/Op18 ( xref )."
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"These findings suggest potential off-target effects of NSC23766 on cell function since effects of NSC23766 are known to be mediated primarily through inactivation of Tiam1 mediated activation of Rac1."
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"Since these fragments lack the dbl domain through which Tiam1 activates Rac1 ( xref ), we reasoned that they would act as dominant-negative inhibitors of GEF-dependent functions of Tiam1 at sites of recruitment to 14–3-3."
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"Studies in neuroblastoma lines demonstrated that over-expression of Tiam1 increases Rac1 dependent neurite outgrowth and insensitivity to RhoA induced neurite retraction."
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"The Rac activator Tiam1 prevents keratinocyte apoptosis by controlling ROS mediated ERK phosphorylation."
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"NSC23766 prevents Rac1 activation by Rac-specific GEFs TrioN and Tiam1, without interfering with the activation of the other Rho-like GTPases (Rho and Cdc42) and has been used to study the functional role of Rac1 [ xref ]."
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"The PI3-kinase–dependent Rac activation by Tiam1, and the subsequent decrease in cell–cell adhesion upon inhibition of PI3-kinase activity, also suggests a role for PI3-kinase in the establishment of E-cadherin–mediated cell–cell adhesion."
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"Rac activation by Tiam1 stimulates cadherin-based cell-cell adhesion in Ras-transformed MDCK cells and NIH 3T3 fibroblasts, limiting their migration and invasion ( Hordijk et al., 1997; Sander et al.,[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"To understand the relationship between the decreased Rac activity and reduced cell migration ability, we verified that NSC23766 (NSC), which selectively blocks Rac activation by Tiam1 ( xref ), also blocked the P-Rex1/Rac1 interaction (see xref )."
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"One possibility may be the activation of Rac by the Rac-specific GEF, Tiam1, which is localized to the TrkB endosomes [ xref ]."
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"Tiam1 mediated Rac Activation Increases Cell-Surface E-cadherin."
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"3) PI3-kinase activity has been implicated in the control of Tiam1 driven activation of Rac1, probably through its effect on the membrane translocation of Tiam1 via the binding of PIP 3 to the TSS domain, including the N-terminal pleckstrin homology domain."
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"The Par complex (Par3, Par6, and PKCzeta) controls cell polarity in part by recruiting the Rac specific guanine nucleotide exchange factor T-lymphoma invasion and metastasis 1 (Tiam1) to specialized cellular sites, where Tiam1 promotes local Rac1 activation and cytoskeletal remodeling."
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"To measure the effect of Bcr on Tiam1 mediated Rac1 signaling in neurons, we utilized the Forster resonance energy transfer (FRET) Rac1 activation biosensor RaichuEV-Rac1."
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"However, the activity of Rac1 was significantly reduced after knocking down Tiam1 expression, indicating that Tiam1 mediates Rac1 activation triggered by NGF (XREF_FIG)."
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"These data suggest that Tiam1 activated Rac1, leads to the nuclear translocation of β-catenin, which then induced cell EMT and metastasis."
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"Tiam1 (T-cell lymphoma invasion and metastasis inducing protein 1), a guanine nucleotide exchange factor that activates Rac, is a colorectal cancer metastasis related gene."
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"XREF_BIBR This is mainly due to the fact that Tiam1 mediated activation of Rac1 regulates both actin cytoskeleton rearrangements as well as cell-cell and cell-matrix adhesions."
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"Based on these findings, these authors concluded that nm23-H1 plays a negative modulatory role in the Tiam1-induced activation of Rac1 [ xref ]."
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"Rac is endocytosed by Rab5 and activated by RacGEF Tiam1 at the early endosome and recycled back to the plasma membrane through Arf6 dependent pathway XREF_BIBR."
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"Tiam1 overexpression is also not sufficient to increase the motility of more poorly motile cells (T-47D) or increase Rac activity."
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"Phosphorylation of Ser 478 in the juxtamembrane region of TrkB by CDK5 (cyclin dependent kinase 5) links TIAM1, a guanine nucleotide exchange factor, to activate Rac1."
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"Because Tiam1 mediated Rac1 activation is a key output of PAR complex signaling, BAI1 could affect this phenomenon."
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"Recent studies from the laboratory of Zheng et al suggested that NSC23766 specifically inhibits Tiam1-induced activation of Rac1, but not Cdc42 or Rho."
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"The Par polarity complex consisting of Par3, Par6, and PKCzeta, in conjunction with Tiam1 mediated Rac signaling, controls apical-basal cell polarity in contacting epithelial cells."
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"i) Defects in the activation of Rac1 in endomembranes: It has been demonstrated that Rac1 is activated in endosomes by its GEF Tiam1, following which it is recycled to the leading edge of migratory cells. xref Since Ocrl1 is involved in endosomal trafficking, xref , xref it is possible that subsequent to Rac1 binding, the Lowe syndrome protein facilitates the activation of the RhoGTPase and perhaps its re-routing to the leading edge."
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"In conclusion, the ability of R-Ras-GTP to convert RIN2 from a GEF to an adaptor that preferentially binds Rab5-GTP allows the triggering of the endocytosis of ECM-bound and active beta1 integrins and the ensuing funneling of R-Ras-GTP toward early endosomes to elicit the pro adhesive and TIAM1 mediated activation of Rac1."
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"Knockdown of Tiam1 by siRNA markedly attenuated PDGF induced migration and proliferation in HASMCs by inhibiting the activation of Rac1."
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"These findings suggest that signaling steps involving Tiam1 mediated activation of Rac1 is relevant for glucose- [XREF_FIG], but not KCl induced insulin secretion from beta-cells."
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"The use of NSC23766 that blocks Rac1 activation by Tiam1, resulted in enhanced LPS- or thrombin-induced endothelial permeability, decreased formation of a stable cortical actin ring at the cell periphery that has been directly correlated with destabilized adherens junctions ( xref ; xref )."
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"Tiam1 specifically activates Rac, and Rac has been shown to affect several signaling pathways in a partly cell-type-specific manner."
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"This Rac1 activation was mediated by G i/o -betagamma and PI3K signaling and by the widely expressed RacGEF Tiam1 (Vettel etal, 2012)."
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"Following EphB activation, Tiam1 induces Rac1 dependent spine formation, whereas Bcr prevents Rac1 mediated receptor internalization, promoting spine growth over retraction."
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"Tiam1 dependent activation of Rac in WT keratinocytes followed the same kinetics as the formation of PAs (XREF_FIG), suggesting that Tiam1 is a downstream target of cadherins and nectins to activate Rac and, thereby, to activate the polarity complex."
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"Tiam1 has previously been shown to direct Rac signalling by binding to other proteins XREF_BIBR XREF_BIBR."
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"From these data, we conclude that Tiam1 mediated Rac activation controls, to a large extent, the chemokine induced polarization of T cells."
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"NSC23766 was demonstrated to bind to Rac1 and to prevent binding to and activation of Rac1 by the Rac1-specific guanine nucleotide exchange factors (GEF) Tiam1 and Trio."
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"Interestingly, it has been demonstrated that Tiam1 and Tiam2 enhance Rac1 activity and are involved in the suppression of RhoA activity in N1E-115 cells [XREF_BIBR]."
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"The precise mechanism that couples NMDA receptor stimulation to Tiam1-dependent Rac1 activation remains to be determined."
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"In turn, Rac1 may be activated by Rac1 GEFs STEF and Tiam1 which are highly expressed in the IZ and CP (Kawauchi et al., xref )."
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"Recent studies from the laboratory of Zheng et al suggested that NSC23766 specifically inhibits Tiam1 induced activation of Rac1, but not Cdc42 or Rho."
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"The concept that the Tiam1 controlled activation of Rac is required for proper cell polarization holds true for both epithelial and neuronal cells."
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"NSC23766 inhibited beta3 integrin mediated CLAN formation by nearly 45% (p = 0.0001) demonstrating a role for Rac1 signaling mediated by either Tiam1 or Trio in CLAN formation."
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"This phenotype is mediated by the guanine nucleotide exchange factor TIAM1, which activates the small GTPase Rac1."
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"Moreover, the FRET analysis of Rac1 in U251 cells showed that the region of higher Rac1 activation sometimes, but not always, overlapped with large adhesions, suggesting that Tiam1 at large adhesion activates Rac1 to control adhesion dynamics for cell migration (see following paragraph)."
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"We also found that expression of betaPIX could not rescue the deficiencies in Rac1 activation and cell spreading caused by Tiam1 depletion (unpublished data)."
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"Importantly, we demonstrate that miR-10b also inhibits Tiam1 mediated Rac activation."
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"Cgnl1 was shown to be an inhibitor of RhoA activity, but was also involved in the activation of Rac1 by the GEF Tiam1 in epithelial cells. xref , xref Like cingulin, Cgnl1 is co-localized with actin filament bundles, implying that it could be a cross-road modulator that links intercellular junction assembly to actin cytoskeleton-regulated morphogenesis, both key processes in angiogenesis."
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"During the preparation of this manuscript, another group reported that VE-cadherin and Tiam1 mediate shear induced Rac1 GTP loading and barrier enhancement in brain microvascular ECs."
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"In the present work, we characterized the domains involved in the MAP1B-Tiam1 interaction, and determined the fragment of MAP1B responsible for Tiam1-dependent Rac1 activation."
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"ROCK1 indirectly diminishes the activity of upstream RhoA by stimulating Tiam1 induced Rac1 activity."
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"These include: (1) PLEKHG6, which displays a GEF activity preferentially on RhoG and interacts with ezrin, (2) KALRN, which relays the message from Arf6 to Rac1 and could interact with PDZ domain cont[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
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"The Rac subfamily GTPases act downstream of the GEFs; CED-10 and Rac1 is activated by TIAM-1, whereas CED-10 and MIG-2 and RhoG act redundantly downstream of UNC-73."
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"Previously, it has been shown that the Rac1 activator Tiam1 regulates the Par3 polarity complex in keratinocytes [XREF_BIBR]."
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"Furthermore, we observed that PA induced generation of lipid peroxides [Panel B] and reactive oxygen species [Panel C] in INS 832/13 cells were also reduced [~ 20 to 30%] following inhibition of Tiam1 mediated activation of Rac1."
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"Functional relevance of GEF [Tiam1 and Vav2] induced Rac1 activation in the generation of oxidative stress, stress kinase activation and mitochondrial dysfunction need to be validated further in islets from animal models and human donors with diabetes."
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"We examined the involvement of Tiam1 and talin in adhesion induced Rac1 activation and cell spreading."
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"One study reported that syndecan-2 regulates colon carcinoma cell migration through Tiam1-dependent Rac activation ( xref )."
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"Our results indicate that they act in a linear pathway, with CDC-42 controlling Rac activity mediated by TIAM-1."
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"Activation of Rac by Tiam1 induces an epithelial-like morphology with functional cadherin-based adhesions and inhibits migration of fibroblasts."
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"This was not altogether surprising, as Tiam1 directs Rac signaling to specific downstream effector pathways, leading to precise defects in Rac signaling, rather than the global Rac defect imposed by Rac silencing."
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"Tiam1 activates RAC1, a subunit of the NADPH oxidase complex (Nox1, Nox2, and Nox3 isoforms), and in turn mediates ROS generation."
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"In conclusion, our data indicate that the Tiam1 mediated activation of Rac (and not the inactivation of Rac) is required for TJ formation in epithelial keratinocytes."
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"These data clearly indicate that Tiam1 DHPH was able to activate Rac1 Ic on the liposomes."
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"Cells overexpressing Tiam1 no longer respond to lysophosphatidic acid- induced neurite retraction and cell rounding, processes mediated by Rho, suggesting that Tiam1 induced activation of Rac antagonizes Rho signaling."
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"The NSC23766 can bind Rac1 preventing Rac1 activation by TrioN and Tiam1 without affecting Cdc42 or RhoA activation [ xref ]."
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"Tiam1 and p190RhoGAP-A, which are associated with Dvl, activate Rac and inhibit Rho, respectively, spatially in regions surrounded by basement membranes."
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"NSC23766 specifically inhibits Rac1 activation by the Rac-specific GEFs Trio or Tiam1 in a dose-dependent manner, but not Cdc42 or RhoA activation by their GEFs."
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"In support of this possibility, both Trio and Tiam1 are expressed in the hippocampus CA1, and interestingly Tiam1 has been shown to mediate NMDA receptor activation of Rac1 in neurons."
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"Through conducting a comparative analysis of Rac1 driven cellular functions upon activation by 2 Rac specific GEFs, Tiam1 and P-Rex1, we provide clear evidence highlighting their role in dictating differential Rac1 dependent cellular processes."
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"Since the inhibition of TJ assembly by over-expressed Tiam1 requires its Rac-GEF activity (XREF_FIG), we hypothesised that beta2-syntrophin promotes Tiam1 mediated Rac activation during TJ assembly."
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"These data provide a mechanism for the regulation of Tiam1 mediated Rac activation in breast cancer cells and need to be considered in the context of other reported functions for miR-10b."
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"Since Tiam1 [XREF_BIBR] and Rac1 are active in the majority of pancreatic cancer cells, Tiam1 might mediate the activation of Rac1."
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"This is a good example that the Rac1 activity is driven by Tiam1 mostly and is regulated dynamically by outside-in signals."
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"The contribution of Tiam1 mediated activation of Rac1 to the upregulation of such tumour promoting genes may represent one mechanism by which the Tiam1 and Rac1 signalling module contributes to tumour development in the colon."
reach
"XREF_BIBR Interestingly, Tiam1 mediated Rac1 activation has been linked to increased transcriptional and post-transcriptional upregulation of Tissue Inhibitor of Metalloproteinase-1 (TIMP-1) and TIMP-2, respectively, while not affecting the secreted levels or activity of Matrix Metalloproteinase-9 (MMP-9) or MMP-2."
reach
"Taken together, these observations indicate that both Tiam1 and talin mediate and are required for the propagation of outside-in signals from integrins to activate Rac1."
sparser
"TIAM1 can activate Rac by phosphatidyl-inositol-3-kinase-dependent or independent mechanisms ( xref ; xref )."
sparser
"It was previously demonstrated that Tiam1 can activate Rac1 and Cdc42 in in vitro exchange assays, and Rac1 in cell-based assays [ xref ]."
reach
"NSC23766, a specific inhibitor of Tiam1 mediated activation of Rac1, but not Cdc42 or Rho, markedly attenuated glucose induced, but not KCl induced, insulin secretion in INS 832/13 cells and normal rat islets [XREF_BIBR]."
reach
"Recent work has established that Tiam1 can activate Rac downstream of LFA-1 in T cells, although it remains unclear whether PIP 3 is involved."
reach
"Association of p110alpha via p85 with VE-cadherin might thereby provide a mechanism by which Tiam-1 is recruited and activates Rac1."
reach
"This indicates that activation of Rac by Tiam1 stimulates the formation or stabilization of functional E-cadherin complexes at the cell surface leading to phenotypic reversion towards an epithelioid phenotype and inhibition of motile and invasive behavior."
reach
"The Rac activator Tiam1 is required for adherens junction (AJ) maintenance, and its depletion results in AJ disassembly."
reach
"XREF_BIBR Functional validation of Tiam1 enriched Rac1 interactors identified from our proteomic screen indicated that Tiam1 mediated activation of Rac1 enhances Rac1-IQGAP1 binding."
reach
"Syndecan-2 regulates cell migration in colon cancer cells through Tiam1 mediated Rac activation."
reach
"Tiam1 mediated Rac Activation Is Regulated by PI3-Kinase."
reach
"Also, a recent report indicates that the cell migration promoted by syndecan-2 occurs through Tiam1 mediated activation of Rac [XREF_BIBR]."
sparser
"The Dbl-family Rho GEF, Tiam1, selectively activates Rac ( Michiels et al. , 1995 )."
reach
"We also discuss additional modes by which Tiam1 and P-Rex1 might induce Rac1 anti- versus pro migratory phenotypes in light of the newly highlighted Rac1 interactors."
reach
"In fibroblasts, Tiam1 induces a similar phenotype as constitutively activated (V12) Rac1, including membrane ruffling, and this is inhibited by dominant negative (N17) Rac1."
sparser
"Collectively, these data strongly suggest that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in colon cancer cells."
reach
"Thus, an alternative mechanism likely explains the role of Tiam1 and Tiam2 in the ROCK1 induced regulation of Rac1 and RhoA activity."
reach
"This suggests, that sustained activation of Rac by Tiam1 resulted in downmodulation of Rho activity."
reach
"Tiam1 and betaPIX mediate Rac dependent endothelial barrier protective response to oxidized phospholipids."
reach
"Indeed, Tiam1 mediated Rac activation induced transcriptional up-regulation of tissue inhibitor of metalloproteinases-1 (TIMP-1) and post-transcriptional up-regulation of TIMP-2, whereas secretion and activity levels of their counterparts, matrix metalloproteinase-9 and matrix metalloproteinase-2, respectively, were not affected."
reach
"Thus, consistent with previous reports, our data strongly suggests that Tiam1 mediated Rac1 anti-migratory effects might be a consequence of stronger cell-cell contacts."
reach
"In fibroblasts, Tiam1 induces Rac mediated membrane ruffling, which requires the N-terminal pleckstrin homology (PHn) domain."
sparser
"Rac activation by Tiam1, however, leads to signaling events that are not necessary for macrophage force generation."
reach
"It has been shown that Tiam1 dependent localized activation of Rac1 contributes to the rapid elongation of the nascent axon XREF_BIBR."
reach
"Our data indicate that Tiam1 mediated activation of Rac in PAs controls TJ biogenesis and polarity in epithelial cells by association with and activation of the Par3-Par6-aPKC polarity complex."
reach
"TIAM1 links activated RAC1 to its effector WASF2 (WAVE2) in lamellipodia through mutual interactions with the adaptor protein BAIAP2."
reach
"Importantly, although additional data we obtained indicated that FLII binds preferentially to active Rac1, Tiam1 mediated Rac1 activation did not enhance Rac1-FLII association, highlighting an additional level of regulation beyond Rac1 activation."
reach
"To investigate whether Tiam1 mediated Rac activation is essential for V12Rap1 induced T cell polarization, we used a dominant negative mutant of Tiam1, corresponding to the PHnCCex domain of Tiam1."
reach
"Surprisingly, Tiam1 induced activation of Rac produces the opposite phenotype : cell spreading and the formation of neurites."
reach
"Kalirin-7 and Tiam1 are also translocated into the postsynaptic region by interacting with the EphB receptor after ephrinB ligand stimulation and enhance Rac activity in the spines."
reach
"Employing data base screening we identified a recently cloned cDNA, KIAA0424, showing substantial sequence homology with Rac activators such as Tiam1, Sos, Vav, and PIX within the catalytic domain."
sparser
"Taken together, these results suggest that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in colon cancer cells."
sparser
"Intriguingly, different extracellular matrices can modulate the biological consequences of Rac activation by Tiam1, a guanine nucleotide exchange factor for Rac."
sparser
"This result suggests that Rac1 activation by Tiam1 largely counteracted the extraction of Rac1 from the liposomes by RhoGDI and shifts Rac1 towards a signaling-competent state."
reach
"Having demonstrated that Tiam1 and P-Rex1 elicit distinct Rac1 driven phenotypes, we were interested in deciphering the mechanism by which these contrasting phenotypes are manifested."
reach
"Tiam1 mediated Rac activation was decreased by dominant negative Deltap85 as well as by PI3-kinase inhibitors on a fibronectin as well as on a collagen I substrate, which argues that Tiam1 activity on both substrates is dependent on lipid products produced by PI3-kinase."
sparser
"The level of Rac activation by Tiam1, as determined by binding to a glutathione-S-transferase– PAK protein, is similar on fibronectin or collagen I, suggesting that rather the localization of the Tiam1/Rac signaling complex determines the substrate-dependent cellular responses."
reach
"To confirm that the observed defect in adhesion and spreading was because of the absence of Tiam1 mediated Rac activation, we introduced full-length Tiam1 and constitutively active Rac1 (V12 or L61 mutants) into Tiam1-/- keratinocytes."
reach
"Together, these data demonstrate that while Tiam1 mediated activation of Rac1 is necessary for GSIS [e.g., data from NSC23766 studies]; data from knock-down experiments indicate that Tiam1 might play additional modulatory role [s] in the events leading to GSIS [see below]."
reach
"Recently, Zheng et al have developed NSC23766, which is a soluble first generation small molecule inhibitor of Tiam1 mediated activation of Rac1 [XREF_BIBR]."
reach
"Here we show that, unexpectedly, Madin-Darby canine kidney epithelial cells depleted of both CGN and CGNL1 (double-KD cells) display normal Rac1 activation and tight junction (TJ) formation, despite decreased junctional recruitment of the Rac1 activator Tiam1."
reach
"Based on these data, Zheng et al concluded that NSC23766 represents a specific inhibitor of Tiam1 mediated activation of Rac1."
sparser
"These results indicate that Rac1 was activated mainly by Rac-GEF Tiam1 in SKBR3 cells; Rac1 activation contributed to PTEN deletion- or IGF-IR overexpressing-caused Trastuzumab resistance; and inhibit[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"Since the Tiam1 mediated Rac activation on each substrate is similar, we suggest that the different intracellular localization of the Rac signaling complex determines whether Rac stimulates E-cadherin-mediated cell-cell adhesion or cell migration."
reach
"The results show that simultaneous down-regulation of Tiam-1 and DOCK180 led to a profound block of C. jejuni induced Rac1 activity."
reach
"Fgd1, Tiam1, and SGEF were used to specifically activate Cdc42, Rac1, and RhoG, respectively, and broad-spectrum Vav2 was used for simultaneous activation of Cdc42, Rac1, and RhoG."
reach
"Another more probable mechanism is that Tiam1 activates Rac1 directly at the plasma membrane."
sparser
"Because TIAM1 is a Rac-specific guanine nucleotide exchange factor ( Worthylake et al., 2000 ), we examined whether EndoA3 affects TIAM1-dependent Rac1 activation."
sparser
"NSC23766 and EHT 1864 both prevent Rac1 activation by the Rac1-specific GEFs Trio and Tiam1 [26,27] , while EHop-016 prevents Rac1 activation via the GEFs Vav1 and, to a lesser extent, Tiam1 [28] ."
reach
"V12Rac or Tiam1 mediated Rac activation resulted in a substantial reduction of Rho activity, leading to an epithelial like morphology."
reach
"Similarly, T cells deficient in the Rac activator Tiam1 are deficient in polarization and locomotion on endothelium, and tend to migrate transcellularly."
reach
"Tiam1 mediated Rac1 activation is not necessary for insulin secretion elicited by a membrane depolarizing concentration of KCl."
reach
"For instance NSC23766 inhibits only Tiam-1 and and Trio activation of Rac, while EHop-016 is a specific inhibitor of the Vav and Rac interaction."
reach
"Our findings indicate that inhibition of Tiam1 mediated activation of Rac1 results in attenuation of glucose-, but not KCl induced insulin secretion from pancreatic beta-cells."
reach
"XREF_BIBR During angiogenic sprouting elicited by angiopoitin-1, which induces collective and directional migration of endothelial cells, a signaling complex that includes beta-catenin and Par3/Par6/PKCzeta is recruited to the cell front to coordinate localized activation of Rac by Tiam1, a Rac specific GEF."
reach
"To investigate whether the substrate dependent phenotypes were due to differences in the degree of Rac activation, we analyzed the level of Tiam1 mediated Rac activation in cells seeded on a fibronectin or collagen I substrate."
reach
"34 The NSC 23766 treatment lead to decreases in the percentage of cells showing ruffling in both cases of ABA and ABA-HP plus H 2 O 2 addition (XREF_FIG), which indicated that the Tiam1 activated Rac1 signaling was indeed involved in the observed H 2 O 2 -induced ruffling."
reach
"HA (mixed sizes) also promotes the interaction between CD44 and several Rac1 specific guanine nucleotide exchange factors [e.g., Tiam1 and Vav2], thereby up-regulating Rac1 (another member of the Rho subclass of the Ras superfamily), leading to altered cytoskeleton mediated cell functions."
sparser
"This phenotype is mediated by the guanine nucleotide exchange factor TIAM1, which activates the small GTPase Rac1."
reach
"From the endosomal membrane, Tiam1 activates Rac1 and thereafter Rac1 is targeted to the plasma membrane in an Arf6 dependent manner to ensure actin dynamics and thus promote cell migration."
reach
"Tiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, was recently identified as a novel colorectal cancer metastasis related gene."
reach
"Tiam1, a typical member of the Dbl like family of GEFs, activates the Rho family GTPase Rac1 [XREF_BIBR]."
reach
"This result suggests that Rac1 activation by Tiam1 largely counteracted the extraction of Rac1 from the liposomes by RhoGDI and shifts Rac1 towards a signaling-competent state."
reach
"PTHrP (parathyroid hormone related peptide)-stimulated cell migration and invasion in colorectal adenocarcinomas is dependent on RAC1 activity, which is augmented by the increased expression of alpha6beta4 integrin and TIAM1 these cells exhibit."
reach
"Rac activation by Tiam1 requires PI3-kinase activity."
sparser
"Tiam1 binds components of the polarity complex and activates Rac upon the formation of PAs."
reach
"Finally, we have shown that Rac signaling is critical for force generation when Rac is activated by Vav1 but not when Rac is activated by Tiam1; these results illustrate the complexity of signaling that occurs upstream of force generation."
reach
"Tiam1 is an activator of the small GTPase Rac1, which directs the actin cytoskeletal remodeling that drives spine and synapse development [XREF_BIBR]."
sparser
"We tested whether or not Rap1 regulates Rac1 activation by exogenous VAV2 and Tiam1 ( xref )."
reach
"Similarly, NME1 has been demonstrated to inhibit RAC1 activity by interacting with the RAC1 activator TIAM1, an effect which is independent of its nucleoside disphosphate kinase activity XREF_BIBR."
sparser
"Here, we report that syndecan-2 regulates cell migration of colon carcinoma cells through Tiam1-dependent Rac activation in Caco-2 cells."
sparser
"While one study reported that a3β1-mediated keratinocyte matrix deposition was dependent on Tiam1-induced Rac1 activation ( xref ), molecular mechanisms were not elucidated."
reach
"Our data thus reveal a prominent role of the alpha (1A)-AR/G (i) betagamma and Tiam1 mediated activation of Rac1 and its effector PAK2 in the induction of hypertrophy in NRCM."
reach
"Tiam1 mediates Ras activation of Rac by a PI (3) K independent mechanism."
reach
"Thus, decreased migration in polyamine depleted cells may be due to the inhibition of Tiam1 activation of Rac1 and the subsequent decreased expression of beta-catenin and E-cadherin leading to reduced cell-cell contacts."
reach
"Based on these findings, these authors concluded that both Vav2 and Tiam1 mediate regulation of Rac1 by linking components of the polarity complex to NADPH oxidase."
reach
"In the absence of Par3, TIAM1 becomes mislocalized causing aberrant activation of Rac, which disrupts normal spine morphogenesis [XREF_BIBR]."
reach
"We have shown that dbcAMP induced Rac1 activation was principally mediated by PKA and Sif- and Tiam1 like exchange factor (STEF)/Tiam2."
reach
"Tiam1 can activate Rac1, but not Cdc42 [XREF_BIBR, XREF_BIBR] and it is involved in T cell trafficking [XREF_BIBR]."
reach
"While Tiam1 appear to mediate NT-3 and BDNF induced Rac1 activation, it is not clear whether activation of Rac1 by Tiam1 is critical for biological responses induced by NGF and TrkA."
sparser
"Thus, decreased migration in polyamine depleted cells may be due to the inhibition of Tiam1 activation of Rac1 and the subsequent decreased expression of beta-catenin and E-cadherin leading to reduced cell-cell contacts."
reach
"Furthermore, experiments using a dominant negative form demonstrate that STEF and Tiam1 mediate extracellular laminin signals to activate Rac1, promoting neurite growth in N1E-115 neuroblastoma cells."
reach
"Tiam1 specifically activates Rac, and earlier studies have demonstrated that Tiam1-Rac signaling affects migration and invasion in a cell type- and cell substrate specific manner."
reach
"Together, these findings provide conclusive evidence to suggest that Tiam1 mediated Rac1 activation is not necessary for KCl induced insulin secretion."
reach
"This indicates that Tiam1 mediated Rac activation does not activate aPKCzeta in protruding astrocytes, as has been shown previously during tight junction formation in keratinocytes."
sparser
"Activation of Rac1 by Tiam1 downregulates RhoA in NIH3T3 fibroblasts and induces strengthening of cadherin-based cell–cell adhesion, with transformation of cells to an epithelial-like morphology with suppressed cell migration capabilities. xref Inversely, activation of RhoA induces migratory and fibroblastic phenotype in NIH3T3 fibroblasts."
reach
"We also quantitated the metabolic cell viability in beta-cells treated with NSC23766 to rule out the possibility that it might exert cytotoxic effects following inhibition of Tiam1 mediated activation of Rac1 in these cells."
reach
"Rac activation was completely inhibited by double knockdown of Asef and Tiam1 (XREF_FIG, left panel)."
reach
"EphBs promote spinogenesis in hippocampal pyramidal neurons via Tiam1 mediated Rac1 activation [XREF_BIBR]."
reach
"Through our work, we confirm that Tiam1 activation of Rac1 stimulates cell-cell adhesion and reduces cell migration."
reach
"Expression of truncated, constitutively active variants of DH-PH-CRD VAV2 or C1199 Tiam1 increased Rac1 GTP content even when endogenous Rap1 was inactivated by Rap1GAP."
reach
"This association led to Tiam1 activation, which in turn increased Rac1 activity and facilitated Eph and ephrin endocytosis."
sparser
"Rac1 GEF Tiam-1 activates Rac1 in endosomes ( xref )."
reach
"The NSC23766 inhibitor that was used, however, specifically blocks Rac1 signaling mediated by the GEFs Tiam1 or Trio."
reach
"Furthermore, we provide evidence that Tiam1 mediates the stimulatory effects of Rac1 on the Wnt responsive transcription factor complex in a Wnt dependent manner."
reach
"Previously, we identified the Rac activator Tiam1 (T-lymphoma invasion and metastasis 1), which plays an important role in Rac mediated E-cadherin-based cell-cell adhesions."
sparser
"Similarly, using an RNA interference-based approach, BDNF-regulated migration of cerebellar granule cell precursors was shown to require Tiam1-dependent activation of Rac ( xref )."
sparser
"Given that EHop-016 can also block Rac1 activation by Tiam1, we sought to determine if this GEF might be involved in phagocytosis."
reach
"Although our findings provide evidence showing that Tiam1 cooperates with Ras to mediate NGF induced Rac1 activation, the residual activity of Rac1 observed in cells treated with Tiam1 RNAi in the presence of NGF, suggests the existence of alternative Tiam1 independent mechanisms through which NGF can activate Rac1."
reach
"Another interesting hit that reduced EphB trans-endocytosis was Abr, a protein that antagonizes Tiam1 stimulated Rac activity downstream ephrinB induced EphB2 forward signaling."
sparser
"Intriguingly, we found that activation of Rac1 by 2 Rac-specific GEFs, Tiam1 and P-Rex1, was associated with differential Rac1-driven cellular effects."
sparser
"We confirmed these results using the small molecule inhibitor NSC23766, which specifically blocks Rac1 activation by Tiam1 ( xref ) ( xref )."
reach
"Since Bcr interacts with Tiam1 and limits Tiam1 induced Rac1 signaling, we hypothesized that Bcr specifically opposes Tiam1 's function at synapses, and that together Tiam1 and Bcr precisely regulate Rac1 activity during spinogenesis."
sparser
"Two of these aptamers were found to inhibit the Tiam1 DHPH-mediated activation of Rac in vitro at low micromolar concentration."
reach
"XREF_BIBR Given the importance of the P-Rex1 scaffolding function in stimulating P-Rex1-specific Rac1 interactions, together with the previously reported scaffolding role of Tiam1, it is likely that the observed Tiam1 mediated modulation of the Rac1 interactome is also a consequence of Tiam1 serving as a scaffolding protein."
reach
"This mutant lacks the catalytic DH domain, still contains the Par3 interaction domain, and inhibits Tiam1 mediated Rac activation."
reach
"Tiam1 activates Rac1 at synapses, and loss of Tiam1 function in neurons uncouples Rac1 activation and spinogenesis from glutamate and NMDA receptor signaling and ephrinB and EphB receptor signaling."
sparser
"To address these limitations we recently performed a study directly comparing the ability of 2 distinct Rac-specific GEFs to regulate Rac1 downstream signaling. xref Focusing on Tiam1 and P-Rex1, which have been associated with contrasting migratory phenotypes, xref we first demonstrated that activation of Rac1 by Tiam1 or P-Rex1, irrespective of cell type or upstream signaling, promotes Rac1 anti- vs. pro-migratory effects, respectively. xref Next, to rigorously evaluate the contribution of GEFs in regulating Rac1 signaling through modulating effector binding, we performed a quantitative proteomic analysis of the Rac1 interactome upon activation by either GEF."
sparser
"From the endosomal membrane, Tiam1 activates Rac1 and thereafter Rac1 is targeted to the plasma membrane in an Arf6-dependent manner to ensure actin dynamics and thus promote cell migration ( xref )."
sparser
"These results demonstrate that Tiam1-induced activation of Rac prevents Rho-dependent neurite retraction and cell rounding."
reach
"XREF_BIBR Focusing on Tiam1 and P-Rex1, which have been associated with contrasting migratory phenotypes, XREF_BIBR we first demonstrated that activation of Rac1 by Tiam1 or P-Rex1, irrespective of cell type or upstream signaling, promotes Rac1 anti- vs. pro migratory effects, respectively."
reach
"TIAM1 activates Rac1 and stimulates neuronal migration by regulating actin cytoskeleton dynamics, and JNK regulates microtubule dynamics by stimulating MAP1B phosphorylation to control neuronal migration [XREF_BIBR]."
sparser
"P-Rex1, Tiam1 and TrioN activated Rac1 Ic to a lower extent ( xref ), particularly TrioN, corresponding to their liposome binding capabilities ( xref )."
reach
"Tiam1 (T lymphoma invasion and metastasis 1), a guanine nucleotide exchange factor that activates Rac, is an important regulator of cell shape and invasiveness in epithelial cells and fibroblasts."
sparser
"It has been reported (1) that syndecan-2 regulates migration of colon cancer cells via Tiam-1-dependent Rac activation [21] , (2) that syndecan-2 controls membrane localization of Tiam-1 [4] , and ([MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"NMDA receptor stimulation has been shown to induce Tiam1 activation, leading to the Tiam1 dependent activation of Rac1 [XREF_BIBR]."
reach
"The cells were modified so that diffusion driven linear gradients XREF_BIBR of a small molecule would induce translocation of the Rac activator Tiam1 to the plasma membrane; this resulted in graded Rac activation across the cell length independent of upstream effectors."
reach
"Similarly, the Par3/6 polarity complex, in conjunction with Tiam1 mediated Rac1 signaling, controls apical-basal cell polarity in contacting epithelial cells."
reach
"Dock2 promotes T cell homing to lymph nodes, whereas Tiam1 mediated Rac activation is associated with T cell adhesion and transendothelial migration."
reach
"Tiam1 (T lymphoma invasion and metastasis-1), a guanine nucleotide exchange factor that activates Rac, was recently identified as a novel colorectal cancer metastasis related gene."
reach
"To determine whether Bcr inhibits Tiam1 induced Rac1 signaling, we expressed Flag tagged Tiam1 in 293T cells with or without Myc tagged Bcr constructs and assessed the effects on Rac1 activation and signaling."
reach
"Tiam1 mediated Rac activity is responsible for polarized outgrowth of protrusions."
reach
"The ability of Tiam1 to induce Rac dependent actin remodeling and cell shape change requires both its Rac-GEF enzymatic activity and its ability to translocate to the plasma membrane, which is mediated by its PHn-CC-Ex domain."
reach
"Our data indicate that the Rac activator Tiam1 contributes to tumorigenicity induced by specific oncogenic signaling pathways only."
sparser
"Tiam1, a typical member of the Dbl-like family of GEFs, activates the Rho-family GTPase Rac1 [ xref ]."
reach
"We demonstrate that Tiam1 mediated Rac activation plays a key role at an early stage of intercellular adhesion to trigger the formation of TJs and, as a consequence, to trigger the polarization of epidermal keratinocytes."
reach
"Similarly, T cells deficient in the Rac activator Tiam1 are deficient in polarization and locomotion on endothelium and tend to migrate transcellularly."
reach
"We show that knockdown of Tiam1 expression with siRNA causes a significant reduction in both Rac1 and neurite outgrowth activity induced by NGF stimulation."
reach
"After LPA or serum stimulation, wild-type fibroblasts are characterized by relatively high Rho activity, whereas Tiam1 expressing cells show decreased levels of Rho activity, as a result of Tiam1 mediated Rac activation (XREF_FIG C, lane 4)."
sparser
"In summary, our data indicate that syndecan-2 regulates cancer cell migration through Tiam1-dependent Rac activation."
reach
"These data support our hypothesis that inhibition of Tiam1 mediated activation of Rac1 leads to inhibition of glucose induced membrane association of Rac1 [XREF_FIG] culminating in inhibition of GSIS under these conditions [XREF_FIG]."
reach
"We demonstrate that Tiam1 specifically activates Rac but not Cdc42 or Rho in NIH3T3 fibroblasts."
sparser
"BCR inactivates TIAM1-activated RAC1 by promoting GTP to GDP hydrolysis of active, GTP-bound RAC1, thus preventing excessive synaptic growth [ 63 ]."
sparser
"Since CaMKII has been shown to phosphorylate Tiam1 and stimulate Tiam1-dependent Rac1 activation ( Fleming et al., 1999 ), we examined whether the NMDA receptor regulates Tiam1 activity via phosphoryl[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
sparser
"It is documented that RhoA activity is relatively high in cultured fibroblasts such as NIH3T3, and activation of Rac by Tiam1 in NIH3T3 cells induces an epithelial-like morphology with functional cadherin-based adhesions ( xref )."
reach
"These defects are accompanied by an impaired targeting of the Rac1 activator Tiam1 at synaptic compartments."
sparser
"Since Pak1/2 are direct effectors of Rac1, we hypothesised that Tiam1-dependent Pak1/2 centrosomal activation was due to Tiam1 activation of Rac1."
sparser
"Bcr therefore serves to restrict Tiam1-induced Rac1 activation to an optimal range that promotes excitatory synapse formation and growth while preventing receptor endocytosis and synapse loss."
reach
"Membrane trafficking between compartments has also been suggested, for example, activation of Rac by Tiam1 on endosomes resulted in protrusive activity on the plasma membrane and cell migration."
reach
"We found that Tiam1 mediated Rac signaling functions in various aspects of tumorigenicity including the formation and progression of Ras induced skin tumors and Wnt induced intestinal tumors."
reach
"Tiam1 mediated activation of Rac was dependent on PI3-kinase, suggesting that PI3-kinase might also play a role in the Tiam1 induced increase of E-cadherin-mediated cell-cell adhesion."
reach
"TIAM1 driven Rac1 activation at the leading edge underpins lamellipodial protrusion XREF_BIBR, XREF_BIBR."
reach
"In addition, the Rac1 specific exchange factor, Tiam1, potentiated the stimulatory effects of Rac1 on the canonical Wnt pathway."
reach
"Tiam1 mediated Rac Activation on Fibronectin and Collagen I Is Similar."
reach
"We conclude that motility triggered by collagen I is stimulated by Tiam1 mediated Rac activation, but only under conditions which prevent E-cadherin-mediated adhesions."
sparser
"Tiam1-dependent activation of Rac in WT keratinocytes followed the same kinetics as the formation of PAs ( xref ), suggesting that Tiam1 is a downstream target of cadherins/nectins to activate Rac and, thereby, to activate the polarity complex."
reach
"Consistent with data from a previous study, we have demonstrated that TIAM1 activates Rac in CRC 44."
sparser
"We propose that Tiam1 activates Rac1 by catalyzing GDP to GTP exchange, and thereby mediates the stimulatory effects of Rac1 on the Wnt-induced transcription factor complex, resulting in the enhanced transcription of a subset of Wnt target genes, including genes that promote unrestricted cell proliferation such as c-Myc and Cyclin D1 ."
sparser
"Association of p110α via p85 with VE-cadherin might thereby provide a mechanism by which Tiam-1 is recruited and activates Rac1."
reach
"Moreover, Tiam1 with a mutation in the Rac activation domain (GEF *), which renders it inactive, was unable to rescue the decrease in P * Pak seen on Tiam1 depletion (XREF_FIG, XREF_SUPPLEMENTARY), strongly suggesting that regulation of centrosomal Pak1/2 activity requires Tiam1 mediated Rac activation."
reach
"Tiam1, which is a Rho-GEF for Rac, was shown to activate Rac by a PI3K independent mechanism XREF_BIBR."
reach
"One of these pathways involves DOCK2 through an unknown mechanism and the other pathway involves Rap1 and the Par polarity complex in conjunction with Rac activators such as Tiam1 or possibly Vav1-3."
reach
"From these data we conclude that PI3-kinase activity is required for Tiam1 mediated activation of endogenous Rac."
reach
"22 Ablation of the Rac1-GEF, Tiam1, reduces metastasis in an ErbB2 mouse model of breast cancer, 23 and loss of Par3 in ErbB2 mouse mammary tumors also promotes invasion and metastasis through Tiam1 mediated Rac1 activation."
reach
"Cdc42 functionalized MNPs concentrated with a magnetic field localized actin polymerization while membrane bound Rac1 signaling was dynamically modulated by bringing MNPs functionalised with the Rac1 activator TIAM1 into and out of membrane proximity."
reach
"Expression of GFP-Dvl2 did not restore Rac1 activity or polarity in Tiam1 depleted cells, whereas expression of Myc-Tiam1 rescued Rac1 activity and partially restored polarity in Dvls depleted cells (XREF_FIG and Supplemental Figures S2, F and H, and S5B)."
sparser
"Western blotting analysis was showed that Tiam1 knockdown decreased the levels of GTP-bound (active) Rac1 in 8505c, whereas Tiam1 overexpression had the opposite effect in TPC-1 cells, suggesting that[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"The GTP exchange factor, Tiam1, when presents at cell membranes, activates Rac1 to initiate a signaling pathway that leads to cytoskeletal remodeling and forms filopodia and lemelopodia."
reach
"In RasV12 transformed cells, persistent Ras signaling results in a Raf and MAP kinase mediated downregulation of the Rac specific exchange factor Tiam1, leading to decreased Rac activity (XREF_FIG)."
reach
"Since translocation of Tiam1 to the plasma membrane promotes the local activation of Rac1 to result in membrane ruffling, we employed a semi-quantitative method to score membrane ruffling activity (see Methods and XREF_SUPPLEMENTARY for quantification method)."
reach
"Furthermore, an N-terminal truncation of mammalian Tiam1, which does not affect the DHPH domains, activates Rac more strongly than full length Tiam1 XREF_BIBR, XREF_BIBR, suggesting that a deleted portion of Tiam1 might normally inhibit GEF activity of the molecule."
reach
"As our results suggest, Tiam1 mediated Rac1 activation may feed back to augment nuclear Wnt signalling, leading to sustained Tiam1 and Rac1 signalling and as a consequence, the enhanced transcription of target genes that may be important for tumour initiation and/or progression."
reach
"In this context, it is interesting to note that Tiam1, a Rac1-GEF, can positively regulate Rac1 activation and neurite outgrowth in NGF differentiated PC12 cells [XREF_BIBR]."
reach
"Tiam1 and Tiam2 activate Rac1 [XREF_BIBR, XREF_BIBR] by stimulating GDP-GTP exchange activity that leads to activated Rac1."
reach
"As it has been shown previously that the dissociation of BCR from Tiam1 augments Rac1 activation, we investigated the impact of OGD on BCR-Tiam1 interactions in co-IP experiments."
reach
"These findings confirm our earlier conclusion that Tiam1 activates Rac downstream of PKCzeta and the Par polarity complex."
reach
"We found that MECs expressing the ANDV N protein had dramatically reduced levels of the RhoA inhibitor p190RhoGAP and the Rac1 activator TIAM1, while levels of IQGAP remained unchanged in N-protein-expressing cells (XREF_FIG)."
reach
"First, the interaction of LC1 and cytoskeleton elements at subcortical domains may recruit Tiam1 promoting Rac1 activation."
sparser
"An additional mechanism driving the RhoGTPase switch is through the interaction between the nucleotide diphosphate kinase–nm23, and the GEF-Tiam1 that activates Rac1 (Fig.  xref b)."
reach
"In contrast to P-Rex1, Tiam1 mediated activation of Rac1 was associated with reduced cell migration."
reach
"From the data obtained in this study we conclude that FAK and Src are rapidly activated upon fibronectin mediated signaling leading to Tiam1 mediated Rac1 activation and that intracellular polyamines influence the signaling strength by modulating interaction of Src with Tiam1 using focal adhesion kinase as a scaffolding site."
reach
"Recently, Zheng et al have developed NSC23766, which is a soluble first generation small molecule inhibitor of Tiam1 mediated activation of Rac1 [XREF_BIBR]."
signor
"Lpa-induced rac activation requires tiam1"
reach
"Together these results suggest that Tiam1 activation of Rac1 is associated with reduced cell migration potentially through its ability to increase actin and cadherin deposition at cell-cell contacts, as previously suggested XREF_BIBR XREF_BIBR."
reach
"In epidermal keratinocytes, the Rac1 activator Tiam1 has been shown to prevent keratinocyte apoptosis after growth factor starvation and heat shock treatment."
reach
"In particular, we report that knockdown of Tiam1 causes a significant reduction in Rac1 activity and neurite outgrowth induced by NGF."
reach
"The clustering of VE-cadherin and beta-catenin at adherens junctions recruits additional proteins that stabilize the junctions including Rac1 along with regulators that increase or maintain Rac1 activity (Tiam1, Vav, IQGAP1), and P190RhoGAP, which inhibits RhoA."
reach
"We also showed that prior incubation of INS-1 832/13 cells with GGTI-2147, an inhibitor of geranylgeranylation of Rac1 or NSC23766, a known inhibitor of Rac1 mediated by Tiam1, a guanine nucleotide exchange factor for Rac1 markedly attenuated cytomix induced ROS generation [XREF_BIBR]."
reach
"Insight into Tiam1 mediated Rac1 anti-migratory effects through modulating Rac1-effector binding."
reach
"For this study we utilized the Rac1 specific inhibitor NSC23766 which blocks a subset of Rac1 signaling mediated by the GEFs Tiam1 and Trio XREF_BIBR."
reach
"Tiam-1 and DOCK180 act cooperatively to trigger Rac1 activation and C. jejuni invasion downstream of FAK."
reach
"Tiam1 specifically activates Rac, and Rac has been shown to affect several signaling pathways in a partly cell-type-specific manner."
reach
"5 Functional activation of Rac1 requires specific guanine exchange factors, including Tiam1 and Sos1, and in diabetes, Tiam1 mediated activation of Rac1 is implicated in retinal Nox2-ROS production."
reach
"Evidence now implicates the Rac activator Tiam1 as a crucial component of the Par complex in regulating neuronal (axonal) and epithelial (apical-basal) polarity."
reach
"First, it is likely that Tiam1, by itself, or Tiam1 activated Rac1 might control activities of putative transcriptional factors that might play negative modulatory roles in GSIS; regulation of cellular function by such factors [e.g., STAT and c-myc] has been described in other cell types [XREF_BIBR, XREF_BIBR]."
reach
"Together these findings indicate that Tiam1 mediated Rac activation is required for the increase in levels of LN5 mRNA and protein upon adhesion of keratinocytes to an exogenous substrate."
reach
"Altogether, these results indicate that LC1 of MAP1B interacts with both PH domains of Tiam1, increasing Rac1 activity."
reach
"To study the effect of Tiam1 mediated Rac activation on migration, we quantified the migratory behavior of control and C1199Tiam1 expressing fibroblast cells using a transwell invasion assay."
reach
"For the OR gate, FKBP, GID1, and YFP were fused to Tiam1, a guanine nucleotide exchange factor that activates Rac1 and results in membrane ruffling when it is recruited to the plasma membrane."
reach
"In particular, Tiam1 activation has been recently linked to the ERBB2 oncogene XREF_BIBR, where Tiam1 mediated Rac activation leads to uncontrolled actin dynamics that may compromise E-cadherin junctions, promoting metastasis XREF_BIBR XREF_BIBR XREF_BIBR."
reach
"Rac1 activation is mediated by Tiam1 XREF_BIBR, whereas Cdc42 activation is mediated by Dbs XREF_BIBR."
reach
"We have previously identified the Rac activator Tiam1 (T-lymphoma invasion and metastasis), which stimulates the strength of intercellular adhesion."
reach
"Previous studies demonstrated that endocytosis is needed for activation of Rac by Tiam1, a signaling pathway critical for migration."
sparser
"Via utilizing Stable Isotope Labeling by Amino acids in Cell culture (SILAC) coupled with StrepII -FLAG Tandem Affinity Purification (SF-TAP), we showed that activation of Rac1 by either Tiam1 or P-Rex1 results in distinct changes in the Rac1 interactome."
reach
"With this in mind, and as a logical extension to our ongoing studies, which provided a compelling evidence for key regulatory roles for Rac1 in GSIS, we undertook the current investigation to determine potential role of Tiam1 mediated Rac1 signaling steps in GSIS in INS 832/13 cells [referred to as beta-cells throughout the manuscript]."
reach
"The Rac activator Tiam1 is required for polarized protrusional outgrowth of primary astrocytes by affecting the organization of the microtubule network."
reach
"We studied therefore, whether the Tiam1 mediated activation of Rac is dependent on PI3-kinase activity."
reach
"Tiam1 localization at the PM should activate Rac and its downstream signaling circuits that lead to formation of ruffling and lamellipodia 22."
sparser
"Activation of Rac by Tiam-1, a GDP-GTP exchange factor for Rac promotes lymphocyte invasions In breast epithelial cells, expression of constitutively active Rac or Cdc42 disrupts the formation of diff[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"Mice deficient in the Rac activator Tiam1 are resistant to Ras induced skin tumours."
reach
"Bcr inhibits Tiam1 induced Rac1 signaling."
reach
"The Tiam1- but not V12Rac mediated migration was reduced three- to fourfold upon inhibition of PI3-kinase, consistent with the effects of PI3-kinase inhibition on the Tiam1 mediated activation of Rac determined in the Rac activity assay."
sparser
"Oncogenic RAS stimulates MP by engaging TIAM1 ( xref ), which activates RAC1 and thereby enhances PM ruffling."
sparser
"These findings confirm our earlier conclusion that Tiam1 activates Rac downstream of PKCζ and the Par polarity complex."
reach
"Most importantly, we have found that the binding of ankyrin (e.g., erythrocyte ankyrin [ANK1], XREF_FIG A, or ANK3 's ARD, XREF_FIG B) to Tiam1 significantly increases the GDP/GTP exchange activity of Rac1 GTPase as compared with untreated Tiam1 mediated Rac1 activation (XREF_FIG C)."
reach
"We accomplished the above objective by two independent approaches; first through the use of NSC23766 to impede the functional activation of Rac1 mediated by Tiam1, and second via the siRNA mediated knock-down of endogenous Tiam1."
sparser
"Tiam1 activates RAC1, a subunit of the NADPH oxidase complex (Nox1, Nox2, and Nox3 isoforms), and in turn mediates ROS generation."
reach
"We have shown previously that full-length Tiam1 (FL1591) or a large COOH-terminal fragment of the Tiam1 protein (C1199) causes Rac1 dependent induction of membrane ruffling in NIH3T3 fibroblast cells."
reach
"This suggested that inhibition of sirtuin activity with the same doses and duration that induced TIAM1 acetylation and decreased Rac1 activation also decreased the GEF activity of TIAM1."
reach
"The level of Tiam1 mediated Rac activation was thus not dependent on the cell substrate, suggesting that rather the different substrate dependent intracellular localization of the Rac activity caused the opposite cellular effects on cell-cell adhesion and motility."
sparser
"Thus, our data suggest that Rac contributes to the progression of melanoma and that Tiam1 may activate Rac in nodular presentations."
sparser
"This indicates that activation of Rac by Tiam1 stimulates the formation or stabilization of functional E-cadherin complexes at the cell surface leading to phenotypic reversion towards an epithelioid phenotype and inhibition of motile and invasive behavior."
reach
"For instance, the GEFs Vav, Sos1, and Tiam1 induce Rac1 signaling in spatially restricted membrane regions enriched in PtdIns (3,4,5) P 3."
reach
"It seems that the particular function of Tiam1 mediated Rac activity identified in this study involves the microtubule cytoskeleton rather than the actin cytoskeleton."
reach
"IOS production by NOX-1 in response to growth factors, and possibly alpha3beta1 integrin stimulation too, requires Tiam1 mediated Rac1 activation in keratinocytes [XREF_BIBR]."
reach
"Similarly, T cells deficient in the Rac activator Tiam1 are deficient in polarization and locomotion on endothelium and tend to migrate transcellularly."
sparser
"Given the key role of Rho GTPases in controlling dendritic arbor and spine development, it is possible that the effects of some of these environmental cues on dendritic development are mediated by Tia[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"This phenotypic transformation of NIH3T3 fibroblasts is due to Tiam1 mediated activation of Rac and Rac mediated downregulation of Rho activity."
reach
"Transfection of dominant negative N17 Cdc42 did not affect the Tiam1 phenotype, consistent with Tiam1 activating Rac rather than Cdc42."
reach
"Similarly, using an RNA interference based approach, BDNF regulated migration of cerebellar granule cell precursors was shown to require Tiam1 dependent activation of Rac."
signor
"This smo-tiam1 complex dissociates upon shh-mediated activation of smo, thus allowing tiam1 to activate rac1."
sparser
"In summary, based on published data and results of this study we propose a scheme of OxPAPC-induced protective effects in the models of VILI, in which OxPAPC triggers Rac activation by Rac-specific GEFs, Tiam1 and Vav2 leading to Rac-dependent activation of tyrosine phosphorylation of p190RhoGAP."
reach
"The involvement of the Rac1 activator Tiam1, a guanine nucleotide exchange factor, as well as the Rac1 effector IQGAP1 has been documented [XREF_BIBR, XREF_BIBR]."
reach
"Most importantly, the binding of HA to CD44v3 of SP1 cells stimulates Tiam1 catalyzed Rac1 signaling and cytoskeleton mediated tumor cell migration."
reach
"TIAM1 can activate Rac by phosphatidyl-inositol-3-kinase-dependent or independent mechanisms."
sparser
"It has been shown that increases in intracellular Ca 2+ and subsequent activation of PKCα generates serine phosphorylation in RhoGDIα, thus inducing membrane translocation and Tiam1-induced activatio[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"Conversely, stimulation of the Epac1-Rap1 pathway by cAMP promotes Tiam1 mediated Rac1 activation, stabilizing cortical actin and junctions between endothelial cells [XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR]."
reach
"Given our findings that Tiam1 mediates the stimulatory effects of Rac1 on Wnt target gene transcription, we sought to determine whether Tiam1 could influence the interaction between Rac1 and beta-catenin."
sparser
"Surprisingly, Tiam1-induced activation of Rac produces the opposite phenotype: cell spreading and the formation of neurites."
reach
"Tiam1 and talin are required for adhesion induced Rac1 activation and cell spreading."
reach
"The production of phosphatidylinositol 3, 4, 5-triphosphate by PI3 kinase has been linked to activation of Rho guanine nucleotide exchange factors such as Sos, Vav, and Tiam1 (Han et al. 1998; Nimnual et al. 1998; Sander et al. 1998), and therefore presumably to Rac or Cdc42 and its effectors such as Pak."
reach
"XREF_BIBR, XREF_BIBR, XREF_BIBR, XREF_BIBR Keratinocytes deficient for the Rac1 activator Tiam1 show increased apoptosis upon growth factor deprivation or heat shock treatment, supporting an anti-apoptotic role of Rac1 in keratinocytes."
sparser
"In addition, NSC23766, which blocks Rac1 activation by the guanine exchange factor Tiam1, increases endothelial permeability [ xref , xref ]."
reach
"Although Tiam1 can act directly as an exchange factor, it can also interact with different membrane and intracellular proteins, which control its GEF activity and determine the outcome signalling of Tiam1 mediated Rac1 activation."
reach
"NSC23766, a specific inhibitor of Tiam1 mediated activation of Rac1, markedly attenuated glucose-, but not KCl induced insulin secretion in INS 832/13 cells and normal rat islets."
reach
"Although the exact mechanism is unknown, NM23-H1 was shown to interact with factors involved in Rac1 activation, such as the small GTPase Arf6 or the nucleotide exchange factor Tiam1 [XREF_BIBR, XREF_BIBR]."
reach
"Consistent with previously described Tiam1 driven formation of Rac1 dependent cell-cell contacts XREF_BIBR, XREF_BIBR, we observe loss of refractile morphology of Tiam1 expressing fibroblasts under brightfield microscopy at high cell densities which hints at altered cell to cell adhesion (XREF_FIG)."
reach
"In addition, Choi et al. [XREF_BIBR] reported that the overexpression of syndecan-2 enhanced migration and invasion of Caco-2 and HCT116 cells through Tiam1 mediated activation of Rac, a GTPase family member involved in cell contact regulation."
sparser
"In this case, activation of Rac by Tiam1 is thought to regulate cellular adhesion via specific subset of integrin receptors."
reach
"Furthermore, Tiam1 is required to activate Rac downstream of the Par complex, presumably to regulate actin remodeling required for T cell polarization."
sparser
"We found that GLS2 binds to Rac1, and inhibits the interaction of Rac1 with its guanine-nucleotide exchange factors (GEFs) such as Tiam1 and VAV1, which would normally activate Rac1."
reach
"In both cases, the effects were due to the TIAM1 mediated activation of RAC1, which, actually, has different effects in the two cell types."
reach
"In contrast to the other liposomes, on which Rac1 Ic was modestly activated by Tiam1, Folch III did not bind Rac1 Ic at all (XREF_FIG)."
reach
"Together, based on the data depicted in XREF_FIG and XREF_FIG, we conclude that Tiam1 mediated activation is necessary for glucose to promote trafficking and membrane association of Rac1 and activation of Rac1 in isolated beta-cells."
sparser
"Because TIAM1 is a Rac-specific guanine nucleotide exchange factor ( xref ), we examined whether EndoA3 affects TIAM1-dependent Rac1 activation."
reach
"P-Rex1, Tiam1 and TrioN activated Rac1 Ic to a lower extent (XREF_FIG), particularly TrioN, corresponding to their liposome binding capabilities (XREF_FIG)."
reach
"These results demonstrate that depletion of Par3 acts through Tiam1 mediated Rac1 activation to induce JNK mediated proliferation in mammary tumors."
reach
"The level of Rac activation by Tiam1, as determined by binding to a glutathione-S-transferase- PAK protein, is similar on fibronectin or collagen I, suggesting that rather the localization of the Tiam1 and Rac signaling complex determines the substrate dependent cellular responses."
reach
"From these data, we conclude that the capacity of Tiam1 to activate Rac is required for proper maturation of intercellular junctions in keratinocytes."
reach
"We next determined potential regulatory effects of Tiam1 mediated Rac1 activation on KCl induced insulin secretion from beta-cells."
sparser
"It is also well established that Tiam1 is capable of activating Rac1 in vitro as a GEF, and induces membrane cytoskeleton–mediated cell shape changes, cell adhesion, and cell motility ( xref ; xref ; xref ; xref )."
sparser
"Rac activation by Tiam1 requires PI3-kinase activity on all substrates."
sparser
"Tiam1 and Tiam2 activate Rac1 [ xref , xref ] by stimulating GDP-GTP exchange activity that leads to activated Rac1."
reach
"HGF attenuates thrombin induced endothelial permeability by Tiam1 mediated activation of the Rac pathway and by Tiam1 and Rac dependent inhibition of the Rho pathway."
sparser
"With the YEA, we were able to reproduce the activation of Rac1, RhoG, Cdc42Hs and RhoA by Tiam-1 [14] , Trio D1 [15] , αPIX [16] and Trio D2 [17] , respectively."
sparser
"PGE 2 ‐induced MEF2 but not PKD activation requires Tiam1‐dependent Rac1 activation."
sparser
"Previous studies demonstrated that endocytosis is needed for activation of Rac by Tiam1, a signaling pathway critical for migration ( xref ; xref )."
sparser
"Another more probable mechanism is that Tiam1 activates Rac1 directly at the plasma membrane."
sparser
"Consistent with data from a previous study, we have demonstrated that TIAM1 activates Rac in CRC xref ."
reach
"As shown in XREF_FIG (lane 1 vs 2-4), knockdown of Tiam1 significantly inhibited the activation of Rac1 compared to cells co-expressing FLT3ITD and scrambled shRNA."
sparser
"As such Vav, Tiam1, SOS [25] and the recently discovered P-Rex1 [26] activate the Rho-GTPase Rac in the presence of PtdIns(3,4,5) P 3 ."
reach
"These findings indicate that Tiam1 not only activates Rac but also contributes to Rac signaling specificity through binding to IRSp53."
sparser
"Tiam1 activates Rac1 at synapses, and loss of Tiam1 function in neurons uncouples Rac1 activation and spinogenesis from glutamate/NMDA receptor signaling and ephrinB/EphB receptor signaling ( xref , xref )."
reach
"Indeed, Tiam1 associates with activated Ras, and these two oncogenes cooperate to activate Rac."
reach
"It is documented that RhoA activity is relatively high in cultured fibroblasts such as NIH3T3, and activation of Rac by Tiam1 in NIH3T3 cells induces an epithelial like morphology with functional cadherin based adhesions."
sparser
"Pervanadate or platelet-derived growth factor induced localized Rac activation dependent on Tiam1 and IRSp53."
reach
"FL-Tiam1, but not Tiam1DeltaDH (XREF_FIG B), could fully restore TJ protein levels in Tiam1KO cells (XREF_FIG A), indicating that the Tiam1 mediated activation of Rac controls the amount of TJ molecules even under conditions in which no TJs are formed."
sparser
"Since Par3 directly interacts with Tiam1 [ xref , xref , xref ], the phosphorylation of Par3 will diminish Rac1 activation by Tiam1 [ xref ]."
reach
"Here, we have analyzed the function of the Rac activator Tiam1 in the control of T-cell trafficking and transendothelial migration."
reach
"In addition, NMDAR downstream pathways of Rac1 activator Tiam1, phosphorylated p21 activated kinase 1, and actin were upregulated in response to the EF."
reach
"Tightly balanced activation of Tiam1 with concurrent deactivation of BCR results in activation of Rac1 and its subsequent downstream effectors."
sparser
"In this study, Rajagopal et al. , [208] showed in fibroblasts that Tiam1-dependent Rac1 activation may be mediated by IRSp53 or spinophilin, depending on the sort of upstream signaling; in fact eac[MISSING/INVALID API KEY: limited to 200 char for Elsevier]"
reach
"Taken together, these results suggest that EphB receptors regulate spine development in part by recruiting, phosphorylating and activating Tiam1, which leads to Rac dependent actin remodeling required for spine formation."
sparser
"NMDA receptor stimulation has been shown to induce Tiam1 activation, leading to the Tiam1-dependent activation of Rac1 [ xref ]."
reach
"Vav2 is required for Rac1 GTP loading, whereas, surprisingly, Tiam1 functions as an adaptor in a VE-cadherin-p67phox-Par3 polarity complex that directs localized activation of Rac1."
sparser
"Expression of V12Rac1 produced a phenotype very similar to that of Tiam1 (Fig. xref , C and D ), which is consistent with earlier observations that Tiam1 activates Rac1."
reach
"In fact, it has been found that addition of certain serum derived lipids (e.g., sphingosine-1-phosphate [S1P] and LPA) to T-lymphoma cells promotes Tiam1 mediated Rac1 signaling and T-lymphoma cell invasion (Stam et al. 1998)."
reach
"The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration."
sparser
"Cells overexpressing Tiam1 no longer respond to lysophosphatidic acid– induced neurite retraction and cell rounding, processes mediated by Rho, suggesting that Tiam1-induced activation of Rac antagonizes Rho signaling."
reach
"In addition, we provide mechanistic evidence of how the RIN2 assisted targeting of R-Ras-GTP onto the Rab5 positive endosomal compartment causes the TIAM1 mediated activation of Rac1, finally promoting EC attachment to the ECM."
reach
"In fibroblasts, Tiam1 mediated Rac activation also resulted in strong inhibition of migration, by increasing cell-cell and cell-matrix adhesions."
reach
"Because Tiam1 activates Rac XREF_BIBR, we wanted to determine if binding of PB1 to S4D elicited this response."
reach
"Apparently, various responses by Tiam1 catalyzed Rac1 signaling may be controlled by selective upstream activators (e.g., availability of certain cytoskeletal proteins [e.g., ankyrin], cell adhesion receptors [e.g., CD44, integrin or E-cadherin], growth activators [e.g., serum, S1P, or LPA] or extracellular matrix components [hyaluronic acid, collagen, or fibronectin, etc.])."