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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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"Tiam1 is a known activator of Rac1, and we show that Tiam1 promotes endothelial cell size, similar to Trio."

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"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 CREDENTIALS: limited to 200 char for Elsevier]"

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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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"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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"Consequently, increased TIAM1 stability promotes RAC1 mediated tumorigenesis [54 *]."

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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."

sparser
"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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"The above findings have immediate relevance to our current findings for potential involvement of Tiam1 mediated Rac1 activation in GSIS."

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"When Par3 is downregulated in neurons, Tiam1 activates Rac1 outside the dendritic spine puncta, producing an increase in the number of immature spines along with a decrease in the number of mature synapses (Zhang and Macara, 2006; Duman et al., 2013) (Figure 3A,B)."

sparser
"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 CREDENTIALS: limited to 200 char for Elsevier]"

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"The Rac1 activator Tiam1 is inhibited by internal interactions."

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"As Tiam1-mediated Rac1 signaling is required for establishing and maintaining cell polarity [14], impaired Tiam1 signaling inhibits the formation of front-rear polarization in migrating cells thereby inhibiting persistent migration [12]."

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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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"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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"As stated above, NSC23766 has been used to specifically inhibit Tiam1 mediated activation of Rac1 in multiple cell types."

sparser
"Tiam1 can activate Rac1, but not Cdc42 [ xref , xref ] and it is involved in T cell trafficking [ xref ]."

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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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"The reliability of this streamlined approach is demonstrated by the creation of an optogenetic Cdc42 GTPase and Rac1-activating Tiam1 GEF protein, which together with our other recently reported technologies, complete a toolbox for spatiotemporally precise induction of Rho-family GTPase signaling at the GEF or GTPase level, for driving filopodial protrusions, lamellipodial protrusions, and cell contractility respectively mediated by Cdc42, Rac1, and RhoA."

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"Thus, Ras mediated TIAM1 activation of Rac1 [XREF_BIBR] may be condition specific, modulated through adhesion and phospholipid signalling."

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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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"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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"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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"In the present study, Tiam1 overexpression activated Rac1, and Rac1 silencing reversed the Tiam1 induced increase in migration and invasion and induction of EMT, suggesting the involvement of the Rac1[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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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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"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 RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels."

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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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"NSC23766 is a cell-permeable specific inhibitor of Rac1 activation by the Rac1-specific GEFs Tiam1 [29]."

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"Association of p110alpha via p85 with VE-cadherin might thereby provide a mechanism by which Tiam-1 is recruited and activates Rac1."

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"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."

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"Active Rab5 increases the recruitment of Tiam1 (a Rac1 guanine nucleotide exchange factor) to early endosomes, allowing the activation of Rac1 [37]."

eidos
"Rac1 is activated by TIAM-1 ( T-cell lymphoma invation and metastasis 1 ) , the guanine exchange factor for Rac1 ."

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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 migrati[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"It has been shown that Tiam1 dependent localized activation of Rac1 contributes to the rapid elongation of the nascent axon XREF_BIBR."

sparser
"Saneyoshi et al. find that stimulation of single spine causes rapid formation of a reciprocally activating signaling complex between CaMKII and a Rac-GEF Tiam1, which stably activates Rac1 and maintains enlarged spine structure during LTP."

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"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."

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"Recently, Zheng et al have developed NSC23766, which is a soluble first generation small molecule inhibitor of Tiam1 mediated activation of Rac1 [XREF_BIBR]."

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"Based on these data, Zheng et al concluded that NSC23766 represents a specific inhibitor of Tiam1 mediated activation of Rac1."

sparser
"Rac1 activation by TIAM1 is an important component of the OPN-CD44-TIAM1-Rac1-mediated mechanism of invasion in bladder cancer cell lines [ xref ]."

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"Tiam1 mediated Rac1 activation is not necessary for insulin secretion elicited by a membrane depolarizing concentration of KCl."

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"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."

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"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 )."

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"We have shown that dbcAMP induced Rac1 activation was principally mediated by PKA and Sif- and Tiam1 like exchange factor (STEF)/Tiam2."

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"Tiam1 can activate Rac1, but not Cdc42 [XREF_BIBR, XREF_BIBR] and it is involved in T cell trafficking [XREF_BIBR]."

eidos
"Tiam1 promotes Rac1 activation and cytoskeletal changes required for metastatic breast tumor cell invasion and migration [ 93 ] ."

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"By activating Rac1 in response to NMDA receptor stimulation, Tiam1 contributes to the actin cytoskeletal remodeling that is required for dendritic arbor growth and spine and synapse development."

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"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."

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"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."

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"Translocation of Tiam1 to the plasma membrane triggers Rac1 activation and downstream signals."

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"Furthermore, we provide evidence that Tiam1 mediates the stimulatory effects of Rac1 on the Wnt responsive transcription factor complex in a Wnt dependent manner."

sparser
"NSC23766 is a cell-permeable specific inhibitor of Rac1 activation by the Rac1-specific GEFs Tiam1 [ xref ]."

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"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."

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"Another RAC1 GEF, TIAM1, colocalizes with the NR1 subunit of the NMDAr and modulates NMDAr-related RAC1-dependent spine morphogenesis, as highlighted by the reduced spine size observed in association with TIAM1 deficiency [69]."
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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_BIBR]."

sparser
"P-Rex1, Tiam1 and TrioN activated Rac1 Ic to a lower extent ( xref ), particularly TrioN, corresponding to their liposome binding capabilities ( xref )."

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"Similarly, the Par3/6 polarity complex, in conjunction with Tiam1 mediated Rac1 signaling, controls apical-basal cell polarity in contacting epithelial cells."

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"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."

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"We show that knockdown of Tiam1 expression with siRNA causes a significant reduction in both Rac1 and neurite outgrowth activity induced by NGF stimulation."

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"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]."

sparser
"Association of p110α via p85 with VE-cadherin might thereby provide a mechanism by which Tiam-1 is recruited and activates Rac1."

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"We demonstrated that Tiam1-mediated Rac1 activation was responsible for the ROS generation through NADPH-dependent oxidases."

sparser
"As mentioned above, Rac1 inhibitor NSC23766 inhibited Rac1 activation by Rac-specific GEFs Trio or Tiam1 [ xref ] in ovarian [ xref ] and cervical cancer [ xref ]."

"Lpa-induced rac activation requires tiam1"

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"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]."

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"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."

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"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."

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"Altogether, these results indicate that LC1 of MAP1B interacts with both PH domains of Tiam1, increasing Rac1 activity."

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."

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"Bcr inhibits Tiam1 induced Rac1 signaling."

sparser
"Oncogenic RAS stimulates MP by engaging TIAM1 ( xref ), which activates RAC1 and thereby enhances PM ruffling."

sparser
"Par-3 also recruits and spatially regulates Tiam1, which activates Rac1, thereby coordinating cytoskeletal remodeling important for the development of cell polarity ( xref )."

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"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."

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"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."

eidos
"DHH promotes filamentous alpha-SMA organization through TIAM1 mediated RAC1 activation Our data demonstrate a critical role for DHH signaling through the primary cilium in the regulation of collagen gel compaction ( Figures 3 and 4 ) and alpha-SMA organization ( Figure 5 , Supplemental Figure 10 ) ."

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"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]."

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"Tiam1 and talin are required for adhesion induced Rac1 activation and cell spreading."

sparser
"Lampugnani and colleagues reported that VE-Cadherin expression increases the total amount of Tiam1 which activates Rac1 ( xref )."

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."

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"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)."

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"These results demonstrate that depletion of Par3 acts through Tiam1 mediated Rac1 activation to induce JNK mediated proliferation in mammary tumors."

sparser
"Since Par3 directly interacts with Tiam1 [ xref , xref , xref ], the phosphorylation of Par3 will diminish Rac1 activation by Tiam1 [ xref ]."

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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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"These data suggest that Tiam1 activated Rac1, leads to the nuclear translocation of beta-catenin, which then induced cell EMT and metastasis.In the present study, we investigated the mechanisms underl[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"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."

sparser
"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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"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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"Tiam1-mediated Rac1 signaling is vital in establishing and maintaining of cell polarity, and it localizes the Rac1 activity at the leading edge of the migrating cells [8]."

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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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"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."

sparser
"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 ."

sparser
"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 CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"In addition, Tiam1 , which encodes a GEF activating Rac1 specifically, is an established Wnt responsive gene ( xref )."

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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 the [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"Given the role of syndecan-4 in the regulation of Rac1 GTPase and the importance of cell migration during muscle regeneration, the aim of our study was to investigate the role of Tiam1-mediated Rac1 activation in syndecan-4-dependent myoblast migration."

sparser
"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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"Tiam1 can then promote Rac1 dependent actin cytoskeletal remodeling required for dendritic spine morphogenesis."

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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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"At the membrane, Tiam1 activates Rac1 and is implicated in cell migration [XREF_BIBR], and whether it is also involved in FA dynamics by virtue of its association with the Syndecan-4 and PAR-3 signaling complex or by binding to PIP 3 at the plasma membrane is yet to be investigated."

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"It has been shown that increases in intracellular Ca 2+ and subsequent activation of PKCalpha generates serine phosphorylation in RhoGDIalpha, thus inducing membrane translocation and Tiam1 induced ac[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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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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"Note that the 14-3-3ζ-Tiam-1-Rac1 and kindlin-talin complexes can occur on the same β-tail, which enables both changes in integrin avidity and affinity.14-3-3ζ in turn bound to the Tiam1 adaptor protein, which further activated the small G protein Rac-1, which regulates the organization of the actin cytoskeleton [65] ."

sparser
"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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"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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"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)."

sparser
"Based on these findings, these authors concluded that nm23-H1 plays a negative modulatory role in the Tiam1-induced activation of Rac1 [ xref ]."

sparser
"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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"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."

sparser
"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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"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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"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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"ROCK1 indirectly diminishes the activity of upstream RhoA by stimulating Tiam1 induced Rac1 activity."

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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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"We examined the involvement of Tiam1 and talin in adhesion induced Rac1 activation and cell spreading."

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"These data clearly indicate that Tiam1 DHPH was able to activate Rac1 Ic on the liposomes."

sparser
"The NSC23766 can bind Rac1 preventing Rac1 activation by TrioN and Tiam1 without affecting Cdc42 or RhoA activation [ xref ]."

sparser
"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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"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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"That PIX acts on Cdc42 and Rac1 in vitro but only Rac1 in vivo is not unexpected; for example, Tiam1, resembling PIX in the DH domain, has been shown to activate Cdc42, Rac1, and RhoA in vitro but is [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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"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."

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"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."

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."

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 CREDENTIALS: limited to 200 char for Elsevier]"

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"The results show that simultaneous down-regulation of Tiam-1 and DOCK180 led to a profound block of C. jejuni induced Rac1 activity."

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"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."

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] ."

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"Thereby, Rac1 activation by Tiam1 can be inhibited."

sparser
"This phenotype is mediated by the guanine nucleotide exchange factor TIAM1, which activates the small GTPase Rac1."

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"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."

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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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"Together, these findings provide conclusive evidence to suggest that Tiam1 mediated Rac1 activation is not necessary for KCl induced insulin secretion."

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"EphBs promote spinogenesis in hippocampal pyramidal neurons via Tiam1 mediated Rac1 activation [XREF_BIBR]."

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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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"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."

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"The NSC23766 inhibitor that was used, however, specifically blocks Rac1 signaling mediated by the GEFs Tiam1 or Trio."

sparser
"Given that EHop-016 can also block Rac1 activation by Tiam1, we sought to determine if this GEF might be involved in phagocytosis."

sparser
"TIAM1 exclusively activates Rac1, and not Cdc42."

eidos
"In different ATL cell lines ( MT-2 and ATL-3I ) , Rac1 was found to be activated by Tiam1 , leading to the formation of lamellipodia and adhesion to stromal cells in in vitro cultures ."

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"NMDA receptor stimulation has been shown to induce Tiam1 activation, leading to the Tiam1 dependent activation of Rac1 [XREF_BIBR]."

sparser
"BCR inactivates TIAM1-activated RAC1 by promoting GTP to GDP hydrolysis of active, GTP-bound RAC1, thus preventing excessive synaptic growth [ 63 ]."

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"These defects are accompanied by an impaired targeting of the Rac1 activator Tiam1 at synaptic compartments."

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."

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"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."

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"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)."

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"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]."

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"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."

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)."

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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_BIBR XREF_BIBR."

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"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."

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"Tiam-1 and DOCK180 act cooperatively to trigger Rac1 activation and C. jejuni invasion downstream of FAK."

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"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]."

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"BCR inactivates TIAM1 activated RAC1 by promoting GTP to GDP hydrolysis of active, GTP bound RAC1, thus preventing excessive synaptic growth [63]."

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"For instance, the GEFs Vav, Sos1, and Tiam1 induce Rac1 signaling in spatially restricted membrane regions enriched in PtdIns (3,4,5) P 3."

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 CREDENTIALS: limited to 200 char for Elsevier]"

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"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."

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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 CREDENTIALS: limited to 200 char for Elsevier]"

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"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)."

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
"Tiam1 and Tiam2 activate Rac1 [ xref , xref ] by stimulating GDP-GTP exchange activity that leads to activated Rac1."

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"Thus, Tiam1 's biological activities are cell- and context dependent; however, under appropriate conditions, Tiam1 mediated Rac1 activation can induce invasive behaviour via effects on the actin cytos[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"PGE 2 ‐induced MEF2 but not PKD activation requires Tiam1‐dependent Rac1 activation."

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 )."

eidos
"Activation of Rac1 by Tiam1 was dependent on the lipid messenger , phosphatidylinositol 5-phosphate ( PtdIns5P ) ."

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."

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
"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."

sparser
"These effects require CD44 binding to TIAM1, which activates Rac1."
| PMC

sparser
"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 ]."

sparser
"Through our work, we confirm that Tiam1 activation of Rac1 stimulates cell–cell adhesion and reduces cell migration."

reach
"DHH promotes filamentous alpha-SMA organization through TIAM1 mediated RAC1 activation."

sparser
"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 ."

reach
"The reliability of this streamlined approach is demonstrated by the creation of an optogenetic Cdc42 GTPase and Rac1-activating Tiam1 GEF protein, which together with our other recently reported technologies, completes a toolbox for spatiotemporally precise induction of Rho-family GTPase signaling at the GEF or GTPase level, for driving filopodial protrusions, lamellipodial protrusions, and cell contractility, respectively mediated by Cdc42, Rac1, and RhoA."

sparser
"Thus, GLS2 blocked the binding of Tiam1 and VAV1 to Rac1-GDP, and inhibited the Rac1 activation by Tiam1 and VAV1."

reach
"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."

sparser
"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."

sparser
"We showed that LC1 is sufficient to promote Tiam1-dependent Rac1 activation."

reach
"It was previously demonstrated that Tiam1 can activate Rac1 and Cdc42 in in vitro exchange assays, and Rac1 in cell based assays [XREF_BIBR]."

reach
"Par-3 also recruits and spatially regulates Tiam1, which activates Rac1, thereby coordinating cytoskeletal remodeling important for the development of cell polarity."

reach
"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."

reach
"The Par complex then activates Tiam1 which itself activates Rac1, resulting in localized actin polymerization in the front."

reach
"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."

reach
"Silencing Tiam1 impaired both ephrinA1 dependent activation of Rac1 and EphA2 endocytosis, definitely establishing Tiam1 as an important modulator of EphA2 signalling."

sparser
"Activation of Rac1 by Tiam1 was dependent on the lipid messenger, phosphatidylinositol 5-phosphate (PtdIns5P)."

reach
"Recent data has demonstrated that RAC1 is activated by the small GEF, TIAM1 (T cell lymphoma Invasion and Metastasis) (69)."

sparser
"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 )."

sparser
"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 ]."

reach
"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."

sparser
"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 )."

sparser
"The precise mechanism that couples NMDA receptor stimulation to Tiam1-dependent Rac1 activation remains to be determined."

eidos
"TIAM1 exclusively activates Rac1 , and not Cdc42 As shown in Figure 4 , PREX1 , TrioN and Vav2 all , to some extent , activate Cdc42 ."

reach
"We also found that expression of betaPIX could not rescue the deficiencies in Rac1 activation and cell spreading caused by Tiam1 depletion (unpublished data)."

sparser
"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."

reach
"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."

eidos
"Namely , NMDAR activation leads to translocation of Rac1 to postsynaptic densities where CaMKII phosphorylates the Rac1GEF kalirin-7 or Tiam1 , which activates Rac1 locally [ 184-187 ] ."
| PMC

reach
"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."

reach
"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
"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."

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."

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
"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
"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
"Rac1 is activated by TIAM-1 (T-cell lymphoma invation and metastasis 1), the guanine exchange factor for Rac1."

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
"Rac1 is activated by TIAM-1 (T-cell lymphoma invation and metastasis 1), the guanine exchange factor for Rac1."

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."

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
"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 CREDENTIALS: limited to 200 char for Elsevier]"

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."

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."

sparser
"Vav2 and Tiam1 activate Rac1, a monomeric G-protein, which subsequently activates multiple signaling pathways that regulate gene expression and promote cell transformation [ xref ]."

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
"This association led to Tiam1 activation, which in turn increased Rac1 activity and facilitated Eph and ephrin endocytosis."

reach
"Tiam1 mediates Rac1 activation and contraction induced glucose uptake in skeletal muscle cells."

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."

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."

reach
"TIAM1 exclusively activates Rac1, and not Cdc42."

reach
"By activating Rac1 in response to NMDA receptor stimulation, Tiam1 may promote actin cytoskeletal remodeling as well as other processes necessary for dendritic arbor growth, spine morphogenesis and sy[MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

sparser
"Tiam1, a typical member of the Dbl-like family of GEFs, activates the Rho-family GTPase Rac1 [ xref ]."

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 CREDENTIALS: limited to 200 char for Elsevier]"

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 ."

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)."

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
"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]."

reach
"The activation of Tiam1/STEF increases the activity of Rac1 at the tip of the axon stimulating the activation of Phosphoinositide 3-kinases (PI3Ks)."

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
"Rac1 activation is mediated by Tiam1 XREF_BIBR, whereas Cdc42 activation is mediated by Dbs XREF_BIBR."

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
"It is noteworthy that the direct relationship between the syndecan-4 coordinated persistent migration and the Tiam1-mediated Rac1 activation remains unknown."

"This smo-tiam1 complex dissociates upon shh-mediated activation of smo, thus allowing tiam1 to activate rac1."

reach
"Most importantly, the binding of HA to CD44v3 of SP1 cells stimulates Tiam1 catalyzed Rac1 signaling and cytoskeleton mediated tumor cell migration."

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
"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
"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."

reach
"We next determined potential regulatory effects of Tiam1 mediated Rac1 activation on KCl induced insulin secretion from beta-cells."

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
"At the membrane, Tiam1 activates Rac1 and is implicated in cell migration [ xref ], and whether it is also involved in FA dynamics by virtue of its association with the Syndecan-4/PAR-3 signaling complex or by binding to PIP 3 at the plasma membrane (Fig. xref c) is yet to be investigated."

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 CREDENTIALS: limited to 200 char for Elsevier]"

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.])."

reach
"Tiam1 and P-Rex1 induce differential Rac1 downstream effects."

reach
"Oncogenic RAS stimulates MP by engaging TIAM1, which activates RAC1 and thereby enhances PM ruffling."

reach
"However, a possible role for this C-PH domain is to promote protein protein contacts with Tiam1 ligands that stimulate Rac1 activity."

sparser
"In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1."

reach
"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."

sparser
"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 CREDENTIALS: limited to 200 char for Elsevier]"

reach
"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."

reach
"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."

reach
"Tiam1, a Rac1 guanine nucleotide exchange factor, is phosphorylated by EphBs and promotes Rac1 dependent actin cytoskeletal remodeling for dendritic spine morphogenesis."

sparser
"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."

reach
"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."

sparser
"This indicates that Tiam1-dependent Rac1 activation is not required for normal centriole duplication or its localisation to the centrosome."

reach
"As Pak1/2 are direct effectors of Rac1, we hypothesized that Tiam1 dependent Pak1/2 centrosomal activation was due to Tiam1 activation of Rac1."

sparser
"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)."

reach
"dbcAMP induced Rac1 activation was principally mediated by protein kinase A (PKA) and Sif- and Tiam1 like exchange factor (STEF)/Tiam2."

reach
"Expression of V12Rac1 produced a phenotype very similar to that of Tiam1, which is consistent with earlier observations that Tiam1 activates Rac1."

reach
"Tiam1 has been shown in tumorigenic cells to activate Rac1 [16,17] and Tiam1 and Rac signaling regulates diverse functions including cell adhesion and migration [18]."

sparser
"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 CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Studies in neuroblastoma lines demonstrated that over-expression of Tiam1 increases Rac1 dependent neurite outgrowth and insensitivity to RhoA induced neurite retraction."

sparser
"These data suggest that Tiam1 activated Rac1, leads to the nuclear translocation of β-catenin, which then induced cell EMT and metastasis."

sparser
"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."

reach
"This Rac1 activation was mediated by G i/o -betagamma and PI3K signaling and by the widely expressed RacGEF Tiam1 (Vettel etal, 2012)."

reach
"Following EphB activation, Tiam1 induces Rac1 dependent spine formation, whereas Bcr prevents Rac1 mediated receptor internalization, promoting spine growth over retraction."

sparser
"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 )."

reach
"Recent studies from the laboratory of Zheng et al suggested that NSC23766 specifically inhibits Tiam1 induced activation of Rac1, but not Cdc42 or Rho."

reach
"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."

reach
"This phenotype is mediated by the guanine nucleotide exchange factor TIAM1, which activates the small GTPase Rac1."

sparser
"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."

sparser
"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 CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Previously, it has been shown that the Rac1 activator Tiam1 regulates the Par3 polarity complex in keratinocytes [XREF_BIBR]."

reach
"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."

reach
"Combining Trio and Tiam1 overexpression has no additive effect on augmenting endothelial cell size, thus leaving open the option that Trio and Tiam1 may act in a linear way to induce Rac1 activity at junctional regions."

reach
"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."

reach
"This is a good example that the Rac1 activity is driven by Tiam1 mostly and is regulated dynamically by outside-in signals."

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."

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
"Thus, an alternative mechanism likely explains the role of Tiam1 and Tiam2 in the ROCK1 induced regulation of Rac1 and RhoA activity."

reach
"TIAM1 links activated RAC1 to its effector WASF2 (WAVE2) in lamellipodia through mutual interactions with the adaptor protein BAIAP2."

reach
"If overexpression of this Tiam1QK mutant in neurons were to lead to a decrease in spine density, this would suggest that Tiam1 promotes spine development by activating Rac1."

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
"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."

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
"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."

sparser
"Rac1 GEF Tiam-1 activates Rac1 in endosomes ( xref )."

eidos
"Vav2 and Tiam1 activate Rac1 , a monomeric G-protein , which subsequently activates multiple signaling pathways that regulate gene expression and promote cell transformation [ 52 ] ."

eidos
"Interestingly , Rab23 was found to be over-expressed in squamous cell carcinoma cells , and it was demonstrated that active Rab23 interacts with beta1 integrin and , through it , with Tiam1 , which mediates Rac1 activation and cell migration and invasion [ 58 ] ( Figure 1e ) ."

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."

eidos
"Tiam1 is a known activator of Rac1 , and we show that Tiam1 promotes endothelial cell size , similar to Trio ."

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 )."

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."

sparser
"Moreover, BDNF-induced Rac1 activation depended on TIAM1, as the induction was blocked by the expression of dominant-negative TIAM1 ( xref )."

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."

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
"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."

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 CREDENTIALS: limited to 200 char for Elsevier]"

reach
"Tiam1 and Tiam2 activate Rac1 [XREF_BIBR, XREF_BIBR] by stimulating GDP-GTP exchange activity that leads to activated Rac1."

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."

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
"Insight into Tiam1 mediated Rac1 anti-migratory effects through modulating Rac1-effector binding."

reach
"The dimeric 14-3-3ζ in turn bound to the Tiam1 adaptor protein, which further activated the small G protein Rac-1, which regulates the organization of the actin cytoskeleton [65]."

eidos
"Par-3 also recruits and spatially regulates Tiam1 , which activates Rac1 , thereby coordinating cytoskeletal remodeling important for the development of cell polarity ( Mertens et al. 2006 ) ."

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
"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
"Thus, Ras-mediated TIAM1 activation of Rac1 [ xref ] may be condition specific, modulated through adhesion and phospholipid signalling."

sparser
"Tiam1 activates RAC1, a subunit of the NADPH oxidase complex (Nox1, Nox2, and Nox3 isoforms), and in turn mediates ROS generation."

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 CREDENTIALS: limited to 200 char for Elsevier]"

reach
"The evidence that the Rac1-GEF Tiam1 is present in dendrites and spines and forms a complex with the NMDA receptor suggests that, by activating Rac1, Tiam1 may mediate some of the effects of the NMDA [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

eidos
"At the membrane , Tiam1 activates Rac1 and is implicated in cell migration [ 71 ] , and whether it is also involved in FA dynamics by virtue of its association with the Syndecan-4 / PAR-3 signaling complex or by binding to PIP3 at the plasma membrane ( Fig. 3c ) is yet to be investigated ."

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
"In both cases, the effects were due to the TIAM1 mediated activation of RAC1, which, actually, has different effects in the two cell types."

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)."

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
"Another more probable mechanism is that Tiam1 activates Rac1 directly at the plasma membrane."

reach
"We used optogenetics to impose activation gradients of either Intersectin-1 (ITSN) or T-Cell Lymphoma Invasion and Metastasis 1 (TIAM1), two GEFs specifically activating Cdc42 or Rac1, respectively."

reach
"Our experiments showed that the amount of active Rac1 had been greatly suppressed while the total expression of Rac1 protein remained unchanged after Tiam1 was knocked down in HASMCs, which suggested [MISSING/INVALID CREDENTIALS: limited to 200 char for Elsevier]"

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
"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 this mechanism, Rac1 is activated by the specific Rac1-GEFs, Tiam1 and STEF and Tiam2 [180,181]."

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."