Affinage

TIAM1

Rho guanine nucleotide exchange factor TIAM1 · UniProt Q13009

Length
1591 aa
Mass
177.5 kDa
Annotated
2026-06-10
100 papers in source corpus 49 papers cited in narrative 49 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

TIAM1 is a Rac1-specific guanine nucleotide exchange factor (GEF) that couples diverse upstream receptors and lipid signals to localized Rac1-driven actin remodeling, governing cell adhesion, polarity, migration, and neuronal morphogenesis (PMID:7753201, PMID:9832565). Its catalytic output toward Rac1 was first defined biochemically in vitro and confirmed by Rac1-dependent membrane ruffling in fibroblasts, where N-terminal truncation unmasks oncogenic transforming activity that is phenocopied by activated Rac1 (PMID:7753201, PMID:8570171). TIAM1 acts as a direct Ras effector through a Ras-binding domain, synergizing with activated Ras to generate Rac-GTP independently of PI3K, and Tiam1-deficient mice are resistant to Ras-induced skin tumorigenesis, establishing it as a physiological proto-oncogene (PMID:12134164, PMID:12075356). GEF activity is gated by phosphoinositides binding the N-terminal PH domain — PtdIns(3,4,5)P3 and PtdIns5P stimulate exchange activity — and by phosphorylation: CaMKII and TrkB-mediated Y829 phosphorylation enhance activity, Cdk1 phosphorylation of S1466 drives centrosomal Pak activation in mitosis, while Src phosphorylation of Y384 creates a Grb2 docking site triggering ERK/calpain-dependent local degradation (PMID:10998360, PMID:24905281, PMID:10212259, PMID:16801538, PMID:26078008, PMID:19285946). TIAM1 levels are further controlled by HUWE1 and CUL3-KBTBD6/7 (the latter requiring GABARAP-mediated membrane recruitment) ubiquitin-dependent degradation (PMID:25543140, PMID:25684205). Spatial control of Rac1 activation is achieved through compartment-specific anchoring: the PHn-CC-Ex domain binds CD44, NMDAR, ephrinBs, and Par3, the PDZ domain binds Syndecan1 and CADM1, and the N-PH domain binds the Arp2/3 p21-Arc subunit, forming a self-amplifying Tiam1-Rac-Arp2/3 module (PMID:19893486, PMID:20361982, PMID:16599904). Within the Par3-Par6-aPKC polarity complex TIAM1 restricts Rac1 activation to control tight junction assembly, apical-basal and front-rear polarity, axon specification, and dendritic spine morphogenesis (PMID:15723052, PMID:15723051, PMID:15721239, PMID:17825562). Non-canonically, TIAM1 forms a nuclear complex with Rac1 and RORγt to drive Il17a transcription in Th17 cells and antagonizes TAZ/YAP by promoting TAZ degradation and blocking TAZ/YAP-TEAD interaction (PMID:27725632, PMID:28416184). Bi-allelic loss-of-function TIAM1 variants cause developmental delay, intellectual disability, and seizures, validated by rescue of the Drosophila sif ortholog (PMID:35240055).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Established TIAM1's core biochemical identity — whether it was an enzyme acting on Rho GTPases — by showing it is a Rac-preferential GEF whose activity drives actin remodeling and oncogenic transformation.

    Evidence In vitro GDS assay and dominant-negative Rac1 epistasis in fibroblasts; N-terminal truncation focus formation assay in NIH3T3

    PMID:7753201 PMID:8570171

    Open questions at the time
    • Did not define the upstream receptors activating Tiam1
    • Did not resolve how the N-terminus autoinhibits the catalytic module
  2. 1997 High

    Connected TIAM1's GEF activity to epithelial biology by showing it localizes to adherens junctions and promotes E-cadherin adhesion while suppressing invasion, framing context-dependent control of motility versus adhesion.

    Evidence Ectopic expression, immunolocalization, and HGF scattering/invasion assays in MDCK cells; PKC-dependent threonine phosphorylation assays

    PMID:9367959 PMID:9407095

    Open questions at the time
    • Mechanism switching Tiam1 between junction stabilization and migration not yet defined
    • Functional consequence of PKC phosphorylation on GEF activity unresolved
  3. 1998 High

    Resolved how upstream signals reach TIAM1 by placing PI3-kinase upstream and showing the Tiam1/Rac response is substrate (ECM)-dependent, with distinct localization in motile versus non-motile cells.

    Evidence Substrate-dependent migration/adhesion assays, PI3K inhibition epistasis, GST-PAK pulldowns, and immunolocalization in epithelial cells

    PMID:9832565

    Open questions at the time
    • Direct PI3K-product engagement by Tiam1 not yet shown biochemically
  4. 1999 High

    Defined post-translational positive regulation by showing CaMKII phosphorylation enhances Tiam1 exchange activity and PP1 reverses it, linking calcium signaling to Rac activation.

    Evidence In vitro CaMKII and PP1 assays with nucleotide exchange readout; intracellular calcium manipulation

    PMID:10212259

    Open questions at the time
    • Specific phosphosites not mapped in this study
    • Magnitude of activation modest (~2-fold)
  5. 2000 High

    Identified the membrane and lipid inputs that activate TIAM1 — direct phosphoinositide binding by the N-PH domain (PtdIns(3,4,5)P3 preferred) and physical scaffolding by CD44v3 and ankyrin — explaining how PI3K and adhesion receptors engage the GEF.

    Evidence Lipid-binding and in vitro GEF assays with domain mutants; co-IP, Scatchard binding, and invasion assays for CD44 and ankyrin

    PMID:10636882 PMID:10893266 PMID:10998360

    Open questions at the time
    • How lipid binding mechanistically relieves autoinhibition not structurally defined
  6. 2002 High

    Placed TIAM1 as a direct Ras effector and demonstrated its in vivo requirement for Ras-driven tumorigenesis, connecting its GEF biochemistry to oncogenic signaling, while also showing scaffold (JIP2/IB2) association directs MAPK pathway specificity.

    Evidence RBD pulldown of GTP-Ras with PI3K-independent Rac-GTP epistasis; Tiam1 KO mice in DMBA/TPA skin model; yeast two-hybrid and kinase assays for JIP2

    PMID:12024021 PMID:12075356 PMID:12134164

    Open questions at the time
    • How Ras-binding integrates with lipid/scaffold inputs unresolved
    • Tissue-specificity of Tiam1 oncogenic requirement not generalized
  7. 2005 High

    Established TIAM1 as the spatially restricted Rac activator within the Par3-Par6-aPKC polarity complex and as the receptor-coupled GEF in neurons, controlling tight junctions, lamellipodia, axon specification, and dendritic/spine morphogenesis.

    Evidence Co-IP, complex reconstitution, genetic epistasis (Par3/Tiam1/Rac), and morphological assays in MDCK cells, hippocampal neurons, and dendrites; NMDAR co-IP and phosphorylation

    PMID:15721239 PMID:15723051 PMID:15723052 PMID:15899863 PMID:16330714

    Open questions at the time
    • How Par3 binding biochemically restrains GEF activity not fully defined
    • Cross-talk between integrin and polarity-complex anchoring unresolved
  8. 2006 High

    Defined receptor-specific activation modes — TrkB-mediated Y829 phosphorylation and EphB-NMDAR recruitment — and a self-amplifying Tiam1-Rac-Arp2/3 module via N-PH/p21-Arc binding, linking TIAM1 to growth-factor and Eph signaling in neurons.

    Evidence Y829F mutagenesis with neurite outgrowth; EphB2-NMDAR co-IP and spine assays; yeast two-hybrid and co-IP for p21-Arc with GEF-dead controls

    PMID:16599904 PMID:16801538 PMID:17440041

    Open questions at the time
    • Quantitative contribution of each receptor input in vivo not partitioned
  9. 2009 High

    Provided structural and degradative regulatory detail — PDZ and PHCCEx domain crystal structures defining partner-binding surfaces and motifs, and the Src→Y384→Grb2→ERK→calpain cascade driving localized Tiam1 degradation at junctions.

    Evidence X-ray crystallography of PDZ and PHCCEx domains with mutational/peptide validation; Y384 mutagenesis, mass spectrometry, and calpain-inhibitor assays

    PMID:19285946 PMID:19893486 PMID:20361982

    Open questions at the time
    • Structure of the full-length autoinhibited GEF not determined
  10. 2010 High

    Uncovered a mitotic role by showing Tiam1-Rac localizes to centrosomes and antagonizes centrosome separation and Eg5, expanding TIAM1 function beyond interphase actin control.

    Evidence Tiam1 siRNA with centrosome separation quantification, monastrol/Eg5 epistasis, and chromosome congression analysis

    PMID:20346677

    Open questions at the time
    • Mitotic activator of centrosomal Tiam1 not identified in this study (resolved 2015)
  11. 2012 Medium

    Refined spatial Rac control by defining talin, β2-syntrophin, and Dvl interactions that establish adhesion-site recruitment and an apicobasal Rac activity gradient opposing apical Par3.

    Evidence Co-IP and direct binding, depletion with Rac activity gradient measurement, and lumen/junction/migration assays in epithelial and neuronal systems

    PMID:23071154 PMID:23103911 PMID:23109420

    Open questions at the time
    • Single-lab interaction data for several partners without reciprocal structural mapping
    • How opposing apical/basal inputs are integrated dynamically unresolved
  12. 2014 High

    Established ubiquitin- and lipid-dependent control of TIAM1 abundance and localization via HUWE1 and CUL3-KBTBD6/7, the latter requiring GABARAP-mediated vesicle recruitment, plus acetylation control by SIRT1/2.

    Evidence Ubiquitylation site mutagenesis and epistasis rescue (HUWE1); KBTBD6/7 knockdown with GABARAP co-IP; acetylation and Rac activity assays (SIRT1/2)

    PMID:24362520 PMID:24905281 PMID:25543140 PMID:25684205

    Open questions at the time
    • Interplay between competing E3 ligases in different compartments not resolved
    • Whether PtdIns5P activation and degradation occur on the same vesicle pools unknown
  13. 2015 High

    Defined the mitotic activator and additional stability control — Cdk1 phosphorylation of S1466 driving centrosomal Pak1/2 activation, and AKT/14-3-3/PP2A bidirectional control of TIAM1 stability downstream of EGFR.

    Evidence S1466 mutagenesis with in vitro Cdk1 assay and Pak epistasis; AKT kinase assay, 14-3-3 co-IP, and PP2A stability assays

    PMID:25746002 PMID:26078008

    Open questions at the time
    • How Cdk1 site phosphorylation couples to Pak activation biochemically not detailed
  14. 2017 Medium

    Revealed non-canonical, compartment-segregated functions — nuclear Tiam1-Rac1-RORγt driving Il17a transcription, and dual cytoplasmic/nuclear antagonism of TAZ/YAP — establishing transcriptional and Hippo-pathway roles distinct from cytoskeletal GEF activity.

    Evidence Nuclear complex co-IP and ChIP with Tiam1 KO EAE model; fractionation, βTrCP/destruction-complex and TEAD interaction assays with CRC invasion readouts

    PMID:27725632 PMID:28416184

    Open questions at the time
    • Whether nuclear functions require GEF catalytic activity not fully dissected
    • Single-lab evidence for each non-canonical mechanism
  15. 2022 Medium

    Linked TIAM1 to human disease and complex physiology — bi-allelic loss-of-function variants causing developmental delay/intellectual disability/seizures, synaptic plasticity in chronic pain-induced depression, and YAP1-TEAD4 transcriptional activation of TIAM1 in cancer invasion.

    Evidence Human genetics with Drosophila sif rescue; conditional KO with electrophysiology/behavior; ChIP and invadopodia assays

    PMID:35240055 PMID:35773411 PMID:36519542

    Open questions at the time
    • Mechanistic basis of seizure/ID phenotype at the neuronal circuit level incomplete
    • Reciprocal YAP-TIAM1 regulation (TIAM1 inhibits TAZ/YAP yet YAP1 activates TIAM1) not reconciled

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many competing inputs (lipids, receptor phosphorylation, scaffolds, E3 ligases, acetylation) are integrated on a single autoinhibited full-length TIAM1 molecule to produce spatially and temporally precise Rac1 activation remains unresolved.
  • No full-length structure showing the autoinhibited-to-active transition
  • Quantitative hierarchy among activating versus degradative inputs unknown
  • Mechanistic relationship between cytoskeletal GEF and nuclear transcriptional roles undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060090 molecular adaptor activity 4 GO:0008289 lipid binding 2 GO:0140110 transcription regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005856 cytoskeleton 3 GO:0005634 nucleus 2 GO:0005815 microtubule organizing center 2 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 5 R-HSA-112316 Neuronal System 4 R-HSA-1640170 Cell Cycle 2 R-HSA-392499 Metabolism of proteins 2 R-HSA-168256 Immune System 1
Partners
CD44DVL1GABARAPHRASPARD3RAC1SDC1TRKB
Complex memberships
EphB2-NMDAR complexPar3-Par6-aPKC polarity complexTiam1-Rac1-RORγt nuclear complexWnt destruction complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Tiam1 functions as a GDP-dissociation stimulator (GDS/GEF) for Rho-like GTPases in vitro, with preferential activity toward Rac1. In fibroblasts, Tiam1 induces membrane ruffling identical to constitutively active V12Rac1, and this phenotype is inhibited by dominant-negative N17Rac1, establishing Tiam1 as a Rac-specific GEF that drives actin cytoskeletal remodeling. In vitro GDS assay; dominant-negative Rac1 inhibition; morphological analysis in fibroblasts Nature High 7753201
1995 N-terminal truncation of Tiam1 activates its oncogenic potential in NIH3T3 cells, establishing Tiam1 as a proto-oncogene whose N-terminal sequences suppress transformation but are required for membrane ruffling. Constitutively active V12Rac1 phenocopies Tiam1-induced oncogenic transformation, placing Rac1 downstream of Tiam1. Overexpression of truncation mutants in NIH3T3 focus formation assay; comparison with V12Rac1 Oncogene High 8570171
1997 Tiam1 localizes to adherens junctions in epithelial MDCK cells, where it promotes E-cadherin-mediated cell-cell adhesion and suppresses HGF-induced cell scattering and invasion. Expression of Tiam1 or RacV12 in Ras-transformed MDCK cells restores E-cadherin adhesion and causes phenotypic reversion. Ectopic expression, immunolocalization, HGF-induced scattering assay, invasion assay in MDCK cells Science High 9367959
1997 Lysophosphatidic acid (LPA) and other agonists induce threonine phosphorylation of Tiam1 in Swiss 3T3 fibroblasts via protein kinase C. PKC inhibition reduces LPA-stimulated Tiam1 phosphorylation by ~75%, and PKC phosphorylates purified Tiam1 on threonine in vitro. In vivo phosphorylation assay; PKC inhibitor Ro-31-8220; PMA treatment; in vitro kinase assay with purified Tiam1 The Journal of biological chemistry High 9407095
1998 The Tiam1/Rac signaling response in epithelial cells is substrate-dependent: on fibronectin/laminin-1 Tiam1 promotes E-cadherin-mediated adhesion and inhibits migration, while on collagen it promotes migration. PI3-kinase acts upstream of Tiam1 and Rac, as PI3K inhibition blocks Tiam1-induced but not V12Rac-induced effects. Tiam1 localizes to adherens junctions in non-motile cells and to lamellipodia in migrating cells. Substrate-dependent migration/adhesion assays; PI3K inhibition; GST-PAK pulldown for Rac-GTP; immunolocalization The Journal of cell biology High 9832565
1999 Both protein kinase Cα and Ca2+/calmodulin-dependent protein kinase II (CaMKII) phosphorylate Tiam1 in vivo. CaMKII phosphorylates Tiam1 in vitro and enhances its nucleotide exchange activity toward Rac1 approximately 2-fold. Protein phosphatase 1 dephosphorylates Tiam1 in vitro and abolishes CaMKII-mediated activation. Intracellular Ca2+ manipulation; in vitro kinase assay (CaMKII); in vitro phosphatase assay (PP1); nucleotide exchange activity assay The Journal of biological chemistry High 10212259
2000 CD44v3 isoform physically associates with Tiam1 in breast tumor cells in vivo. The PHn-CC-Ex domain (aa 393–738) of Tiam1 is the primary CD44-binding region (Kd ~0.2 nM by Scatchard analysis). HA binding to CD44v3 stimulates Tiam1-catalyzed Rac1 activation and cell migration; disrupting CD44-Tiam1 interaction with the PHn-CC-Ex fragment blocks both. Co-immunoprecipitation; in vitro binding assay with recombinant fragment; Scatchard plot; Rac1 activation assay; migration assay The Journal of biological chemistry High 10636882
2000 Ankyrin binds directly to Tiam1 via the ankyrin repeat domain (ARD), and the 11-aa sequence aa717-727 of Tiam1 is the ankyrin-binding domain. Ankyrin binding to Tiam1 activates GDP/GTP exchange on Rac1. Blocking this interaction with a Tiam1 fragment (aa393-728) inhibits Rac1 activation and breast tumor cell invasion. Co-immunoprecipitation; deletion mutation analysis; in vitro binding assay; GEF activity assay; tumor invasion assay The Journal of cell biology High 10893266
2000 The N-terminal pleckstrin homology (N-PH) domain of Tiam1 binds phosphoinositides with rank order PtdIns(3,4,5)P3 > PtdIns(3,4)P2 >> PtdIns(4,5)P2. PtdIns(3,4,5)P3 and PtdIns(3,4)P2 enhance Tiam1 GEF activity in vitro. The N-PH domain is required for PI3K-dependent Rac1 activation and membrane ruffling in cells. Lipid-binding assay; in vitro GEF activity assay; co-expression with constitutively active PI3K; domain deletion mutants The Biochemical journal High 10998360
2001 Tiam1 localizes to microtubules in the nascent axon growth cone of cultured neurons. Overexpression of Tiam1 induces formation of multiple axon-like neurites, whereas suppression of Tiam1 prevents axon formation and growth cone cytoskeletal reorganization, indicating Tiam1 regulates axon specification through Rac1-dependent actin organization. Tiam1 overexpression and suppression; immunolocalization; cytochalasin D treatment; neuronal morphology analysis The Journal of neuroscience Medium 11264310
2002 Tiam1 preferentially associates with activated GTP-bound Ras through a Ras-binding domain (RBD). Activated Ras and Tiam1 cooperate to produce synergistic Rac-GTP formation in a PI3K-independent manner, establishing Tiam1 as a direct Ras effector that mediates Ras activation of Rac. GST pulldown of GTP-Ras with Tiam1 RBD; Rac-GTP measurement (PAK-PBD pulldown) with PI3K inhibitors; co-expression of activated Ras and Tiam1 Nature cell biology High 12134164
2002 Tiam1-deficient mice are resistant to Ras-induced skin tumorigenesis. Loss of Tiam1 is associated with increased apoptosis during tumor initiation and impeded proliferation during promotion. Tiam1-deficient primary embryonic fibroblasts resist RasV12-induced focus formation. Tumor number was Tiam1 gene-dose dependent. Tiam1 knockout mice; DMBA/TPA skin tumor model; focus formation assay with primary MEFs Nature High 12075356
2002 The N-terminal region of Tiam1 (containing PH domain, coiled-coil, and additional sequences) binds the scaffold protein IB2/JIP2. IB2/JIP2 simultaneously binds MLK3, MKK3, and p38 MAPK. Tiam1 binding to IB2/JIP2 potentiates p38 MAP kinase cascade activation but not JNK activation, revealing that scaffold association directs Rac signaling specificity. Yeast two-hybrid; co-immunoprecipitation; p38/JNK kinase assays; domain-deletion mapping Molecular and cellular biology Medium 12024021
2004 Tiam1 interacts with ephrin-B1 and EphA2 and mediates Rac1 activation and neurite outgrowth in response to both ephrin-B1 reverse signaling (via clustered EphB2) and EphA2 forward signaling (via ephrin-A1). Dominant-negative Tiam1 blocks neurite outgrowth induced by these Eph/ephrin signals. Co-immunoprecipitation; Rac1 activation assay; dominant-negative Tiam1 inhibition; neurite outgrowth assay in cortical neurons and neuroblastoma cells The EMBO journal Medium 14988728
2004 Tiam1 is required for the formation and maintenance of cadherin-based adherens junctions in MDCK cells. siRNA-mediated knockdown of Tiam1 causes junction disassembly and acquisition of a mesenchymal migratory phenotype. E1A-induced epithelial reversion requires Tiam1 upregulation and Rac activation. siRNA knockdown; E1A expression; Rac activation assay; Tiam1 KO primary MEFs The Journal of biological chemistry High 15138270
2005 Par-3 directly binds the C-terminal region of Tiam1. Knockdown of Par-3 leads to constitutive Rac activation and disrupted tight junction assembly; this is rescued by dominant-negative Rac or by Tiam1 knockdown. Thus Par-3 spatially restrains Tiam1-mediated Rac activity to control tight junction assembly. Co-immunoprecipitation; Par-3 siRNA knockdown; dominant-negative Rac rescue; Tiam1 siRNA; tight junction formation assay Nature cell biology High 15723052
2005 PAR-3 directly interacts with STEF/Tiam1 and recruits them into the PAR-3-aPKC-PAR-6-Cdc42-GTP complex. This complex mediates Cdc42-induced Rac activation and lamellipodia formation. Disrupting PAR-3-STEF/Tiam1 interaction inhibits Cdc42-induced lamellipodia but not filopodia. STEF/Tiam1 accumulates at the axon tip and is required for neuronal polarity. Co-immunoprecipitation; complex reconstitution; dominant-negative disruption; lamellipodia/filopodia morphology assay; hippocampal neuron imaging Nature cell biology High 15723051
2005 Tiam1 is present in dendrites and spines and interacts with the NMDA receptor. NMDA receptor stimulation induces calcium-dependent phosphorylation of Tiam1. RNAi knockdown and dominant-interfering Tiam1 mutants impair dendritic arbor and spine development via Rac1-dependent actin remodeling. Co-immunoprecipitation with NMDAR; in vivo phosphorylation assay; RNAi knockdown; dominant-negative Tiam1; dendritic morphology analysis Neuron High 15721239
2005 Tiam1 is required for alpha3beta1 integrin-mediated Rac activation, laminin-5 deposition, cell spreading, and migration in keratinocytes. Tiam1-deficient keratinocytes cannot activate Rac upon alpha3beta1-mediated adhesion and cannot deposit their own LN5 substrate. Tiam1 or V12Rac1 rescues these defects. Tiam1 KO keratinocytes; Rac activation assay (GST-PAK pulldown); V12Rac1 rescue; wound healing/migration assay in vivo The Journal of cell biology High 16330714
2005 Tiam1 binds to IRSp53 (an adaptor/effector for Rac and Cdc42). Tiam1 directs IRSp53 preferentially to Rac signaling by enhancing its interaction with active Rac and the WAVE2 scaffold, promoting IRSp53 localization to lamellipodia over filopodia. IRSp53 depletion prevents Tiam1-dependent lamellipodia formation. Co-immunoprecipitation; IRSp53 siRNA depletion; subcellular localization by immunofluorescence; lamellipodia/filopodia morphology assay Molecular and cellular biology Medium 15899863
2005 Tiam1 is a Wnt-responsive gene: its expression is up-regulated in intestinal crypts by the canonical Wnt/APC pathway. Tiam1 deficiency in APC-mutant Min mice significantly reduces polyp formation and growth, but enhances malignant invasion, indicating Tiam1 promotes Wnt-driven tumor initiation/growth while restraining malignant conversion. Tiam1 KO × Min mouse cross; polyp counting; Tiam1 siRNA in human CRC cells; Wnt reporter assay The Journal of biological chemistry High 16249175
2006 PAR-3 binds TIAM1 and spatially restricts it to dendritic spines in hippocampal neurons. Depletion of PAR-3 causes formation of multiple filopodia- and lamellipodia-like protrusions resembling activated Rac, indicating that PAR-3 limits TIAM1-mediated Rac-GTP levels to enable proper spine morphogenesis. PAR-3 RNAi; TIAM1 co-immunoprecipitation; spine morphology analysis in hippocampal neurons Nature cell biology High 16474385
2006 Tiam1 interacts with the p21-Arc subunit of the Arp2/3 complex via its N-terminal PH domain and adjacent coiled-coil region. Tiam1 co-localizes with Arp2/3 at sites of actin polymerization. Deletion of the p21-Arc-binding domain impairs Tiam1 localization and Rac1 activation. Functionally active Tiam1 (but not GEF-deficient mutant) promotes Arp2/3 activation, revealing a self-amplifying Tiam1-Rac-Arp2/3 module. Yeast two-hybrid; co-immunoprecipitation; domain deletion; immunofluorescence co-localization; Rac1 activation assay; WASP inhibitor The Biochemical journal High 16599904
2006 TrkB directly binds Tiam1 and phosphorylates Tyr-829 in response to BDNF stimulation, leading to Rac1 activation and lamellipodia formation. A Y829F point mutation in Tiam1 blocks BDNF-induced morphological changes and neurite outgrowth. Co-immunoprecipitation; site-directed mutagenesis (Y829F); Rac1 activation assay; neurite outgrowth assay Proceedings of the National Academy of Sciences of the United States of America High 16801538
2007 The Par-Tiam1 complex (Par3, Par6, PKCzeta, Tiam1) localizes to leading edges of migrating keratinocytes. Tiam1-deficient and Par3-depleted keratinocytes migrate randomly due to failure to maintain front-rear polarity. Par-Tiam1 stabilizes front-rear polarity by stabilizing microtubules; Tiam1 KO cells have unstable microtubules that impair directional but not random migration. Tiam1 KO and Par3 siRNA keratinocytes; chemotaxis assay; live cell imaging; immunoprecipitation; microtubule stability assay Current biology High 17825562
2007 EphB receptor activation by ephrinB1 induces tyrosine phosphorylation and recruitment of Tiam1 to EphB2-NMDAR complexes in a kinase-dependent manner. RNAi knockdown or dominant-negative Tiam1 blocks ephrinB1-induced dendritic spine formation, placing Tiam1 downstream of EphB in Rac1-dependent spine morphogenesis. Co-immunoprecipitation; tyrosine phosphorylation assay; RNAi knockdown; dominant-negative Tiam1; spine density analysis Proceedings of the National Academy of Sciences of the United States of America High 17440041
2008 Paracingulin physically interacts with Tiam1 and GEF-H1 in vivo and in vitro, and is required for their efficient recruitment to epithelial junctions. Paracingulin depletion reduces Rac1 activity in a Tiam1-dependent manner during tight junction assembly and delays junction formation. Co-immunoprecipitation; in vitro binding; siRNA knockdown; immunofluorescence; Rac1 activity assay Molecular biology of the cell Medium 18653465
2009 Src phosphorylates Tiam1 on Y384, predominantly at adherens junctions. This creates a docking site for Grb2, leading to recruitment of the Grb2-Sos1 complex, ERK activation, and localized calpain-dependent degradation of Tiam1 at AJs, resulting in junction disassembly, cell migration, and EMT. Site-directed mutagenesis (Y384); mass spectrometry; co-immunoprecipitation; ERK activation assay; calpain inhibitor treatment; tumor tissue correlation Molecular cell High 19285946
2009 The Tiam1 PDZ domain adopts a canonical PDZ fold (crystal structure determined) and binds Syndecan1 C-terminal peptide. Syndecan1 is a physiological Tiam1 binding partner; the PDZ domain mediates cell-matrix adhesion and cell migration. X-ray crystallography; NMR chemical shift perturbation; equilibrium binding; mutagenesis; cell-matrix adhesion assay Journal of molecular biology High 20361982
2009 Crystal structure of the Tiam1/2 PHCCEx domain reveals a single globular domain comprising a PH subdomain, antiparallel coiled-coil (CC), and novel three-helical Ex subdomain. Mutational analysis shows CC and Ex subdomains form a positively charged surface for protein binding. Two acidic motifs in binding partners (Motif-I in CD44, ephrinBs, NMDAR; Motif-II in Par3, JIP2) mediate PHCCEx interaction. X-ray crystallography; mutational binding analysis; peptide competition assays The EMBO journal High 19893486
2010 Tiam1 and Rac1 localize to centrosomes during prophase and prometaphase. Tiam1-Rac signaling retards centrosome separation and antagonizes Eg5 (kinesin-5). Tiam1-depleted cells escape monopolar arrest caused by Eg5 inhibition, display slower prometaphase transit, and show increased chromosome congression errors. This identifies Tiam1-Rac as the first antagonist of centrosome separation during prophase. Tiam1 siRNA depletion; centrosome separation quantification; Eg5 inhibitor (monastrol); chromosome congression analysis; immunofluorescence at centrosomes Current biology High 20346677
2011 The Tiam1 and Tiam2 PDZ domains have overlapping but distinct ligand specificities determined by four non-conserved residues in the S0 and S-2 pockets. A Tiam1 PDZ quadruple mutant acquires Tiam2 PDZ specificity, revealing the molecular determinants of ligand selectivity. Combinatorial peptide library screening; equilibrium binding assays; site-directed mutagenesis; double mutant cycle analysis Biochemistry High 21192692
2012 Tiam1 interacts directly with talin, which links integrins to signaling. Tiam1 accumulates at adhesions dependent on talin and the PAR complex. Talin-Tiam1 and PAR complex interactions are required for adhesion-induced Rac1 activation, cell spreading, migration toward integrin substrates, and adhesion turnover. Co-immunoprecipitation; direct binding assay; Rac1 activation assay; cell spreading and migration assays; adhesion turnover measurement The Journal of cell biology Medium 23071154
2012 β2-syntrophin binds Tiam1 and promotes Tiam1-Rac activity at basal cell-cell junctions, generating an apicobasal Rac activity gradient. In contrast, apical Par-3 inhibits Tiam1-Rac activity. This gradient is required for optimal tight junction assembly and apical lumen formation. Co-immunoprecipitation; β2-syntrophin depletion; Rac activity assay; TJ assembly assay; lumen formation assay; constitutively active Rac targeting Nature cell biology High 23103911
2012 Tiam1 regulates the Wnt/Dvl/Rac1 pathway in midbrain dopaminergic neurons: Tiam1 interacts with Dvl, facilitates Dvl-Rac1 interaction, and is required for Wnt5a/Dvl-induced Rac1 activation. CK1 negatively regulates Tiam1-Dvl interaction. Tiam1 knockdown impairs DA neuron generation in ventral midbrain neurosphere cultures. Co-immunoprecipitation; Rac1 activation assay; Tiam1 knockdown; neurosphere cultures; DA neuron counting Molecular and cellular biology Medium 23109420
2013 CADM1's cytoplasmic domain (type II PDZ-binding motif) directly interacts with the PDZ domain of Tiam1 in ATL cells. This interaction induces lamellipodia formation through Rac activation, promoting leukemic cell invasion. Amino acid alignment; direct binding assay; co-immunoprecipitation; lamellipodia morphology; Rac activation assay The Journal of biological chemistry Medium 20215110
2013 NMDA receptor stimulation promotes oligodendrocyte precursor cell (OPC) migration via the Tiam1/Rac1/ERK signaling pathway. Tiam1 co-immunoprecipitates with NMDAR in OPCs. Pharmacological inhibition or shRNA knockdown of Tiam1 abolishes NMDAR-promoted migration. Co-immunoprecipitation; shRNA knockdown; Rac1/ERK activation assays; Boyden transwell and single-cell migration assays; brain slice culture Glia Medium 24123220
2013 SIRT1 and SIRT2 positively regulate TIAM1 activity and Rac1-GTP levels. SIRT1/2 inhibition leads to increased acetylation of TIAM1. SIRT1 maintains Dishevelled-1 (DVL1) levels to sustain a DVL1-TIAM1 scaffolding complex that promotes Rac activation. Diminished sirtuin activity disrupts DVL1-TIAM1 interaction. Co-immunoprecipitation; TIAM1 acetylation assay; Rac1 activity assay; SIRT1/2 inhibition; siRNA knockdown Oncogene Medium 24362520
2014 HUWE1 E3 ubiquitin ligase ubiquitylates TIAM1 and targets it for proteasomal degradation, predominantly at cell-cell adhesions during HGF-induced scattering. Depletion of HUWE1 or mutation of the TIAM1 ubiquitylation site prevents TIAM1 degradation and antagonizes scattering and invasion. Simultaneous TIAM1 depletion restores migration in HUWE1-depleted cells. Ubiquitylation assay; proteasome inhibitor; HUWE1 knockdown; TIAM1 ubiquitylation site mutagenesis; scattering/invasion assay; lung cancer cell invasion assay Cell reports High 25543140
2014 Phosphatidylinositol 5-phosphate (PtdIns5P) binds the DH-PH domains of Tiam1 and activates its GEF activity. In a reconstituted assay with membrane-anchored Rac1-His and PtdIns5P-containing liposomes, intrinsic Tiam1 DH-PH activity is enhanced by the PtdIns5P-enriched environment. This pathway is operative in receptor tyrosine kinase activation, bacterial IpgD expression, and NPM-ALK+ lymphoma invasion. Lipid-binding assay; in vitro GEF activity reconstitution with liposomes; Rac1-His membrane anchoring assay; cell invasion assay Nature communications High 24905281
2015 AKT (downstream of EGFR/PI3K) phosphorylates TIAM1 at consensus phosphorylation sites, facilitating interaction with scaffold proteins 14-3-3 and increasing TIAM1 protein stability. TIAM1 is subsequently dephosphorylated and destabilized by PP2A, defining a bidirectional phosphorylation/dephosphorylation mechanism controlling TIAM1 stability and EGFR-driven Rac1 activation. AKT in vitro kinase assay; 14-3-3 co-immunoprecipitation; PP2A inhibitor/overexpression; protein stability assay; TIAM1 knockdown Oncogene Medium 25746002
2015 The CUL3-KBTBD6/KBTBD7 ubiquitin ligase complex mediates ubiquitylation and proteasomal degradation of TIAM1. KBTBD6/7 employ ATG8-family-interacting motifs to bind GABARAP proteins. TIAM1 ubiquitylation depends on its binding to GABARAP proteins on vesicles, thereby spatially restricting membrane-associated TIAM1 and RAC1 signaling. Ubiquitylation assay; KBTBD6/7 knockdown; GABARAP co-immunoprecipitation; proteasome inhibitor; Rac1 activity assay; actin morphology analysis Molecular cell High 25684205
2015 Cdk1 phosphorylates Tiam1 on S1466 during mitosis. This phosphorylation is required for activation of group I p21-activated kinases (Pak1 and Pak2) on centrosomes in prophase. Pak1 and Pak2 counteract centrosome separation downstream of Tiam1, and Pak1/2 depletion allows cells to escape monopolar arrest by Eg5 inhibition. Site-directed mutagenesis (S1466); in vitro Cdk1 kinase assay; centrosome Pak activation assay; siRNA knockdown of Pak1/2; monopolar arrest assay Nature communications High 26078008
2016 Tiam1 and Rac1 form a complex with the transcription factor RORγt in the nucleus of Th17 cells and together bind and activate the Il17a promoter. Tiam1 genetic deficiency weakens IL-17A expression and attenuates experimental autoimmune encephalomyelitis (EAE). Co-immunoprecipitation of nuclear Tiam1-Rac1-RORγt complex; ChIP assay at Il17 promoter; Tiam1 KO mice; EAE model; pharmacological Rac1 inhibition Nature communications Medium 27725632
2017 TIAM1 antagonizes TAZ/YAP by two spatially distinct mechanisms: (1) in the cytoplasm, TIAM1 localizes to the destruction complex and promotes TAZ degradation by enhancing its interaction with βTrCP; (2) in the nucleus, TIAM1 suppresses TAZ/YAP interaction with TEAD transcription factors, inhibiting EMT-related gene expression and CRC cell invasion. Nuclear/cytoplasmic fractionation; co-immunoprecipitation of TIAM1 with destruction complex and βTrCP; TEAD interaction assay; TAZ degradation assay; CRC cell invasion assay Cancer cell High 28416184
2018 EndoA3 (endophilin A3) binds TIAM1 directly, and this interaction competes with EndoA3 membrane binding. When EndoA3-membrane interaction is disrupted, TIAM1 binding is favored, leading to TIAM1 and small GTPase activation and increased cell motility/metastasis in vivo. Direct binding assay (EndoA3-TIAM1); competition with membrane liposomes; GTPase activation assay; in vivo metastasis model in zebrafish Developmental cell Medium 29920278
2022 Tiam1 orchestrates synaptic structural and functional plasticity in anterior cingulate cortex (ACC) neurons via actin cytoskeleton reorganization and synaptic NMDAR stabilization. Tiam1-mediated synaptic plasticity drives ACC hyperactivity underlying chronic pain-induced depressive-like behaviors. Ketamine blocks Tiam1-mediated maladaptive synaptic plasticity to produce antidepressant-like effects. Tiam1 conditional KO; electrophysiology; spine morphology imaging; actin dynamics assay; NMDAR surface expression; chronic pain mouse models; behavioral assays The Journal of clinical investigation Medium 36519542
2022 Loss-of-function variants in TIAM1 (bi-allelic missense) cause developmental delay, intellectual disability, and seizures. In Drosophila, loss of the ortholog still life (sif) reduces survival, causes climbing defects and seizures. Human TIAM1 reference cDNA partially rescues sif loss-of-function phenotypes; patient variants show reduced rescue ability confirming partial loss of function. Human genetics (bi-allelic variants in patients); Drosophila sif KO; in vivo rescue with TIAM1 reference vs. patient variant cDNAs; ectopic expression toxicity assay American journal of human genetics High 35240055
2022 YAP1-TEAD4 transcriptionally activates TIAM1 expression by binding to an enhancer region of the TIAM1 gene. TIAM1 upregulation increases RAC1 activity and induces invadopodia formation in breast cancer cells. ChIP assay for TEAD4 at TIAM1 enhancer; YAP1 knockdown/overexpression; TIAM1 expression measurement; RAC1 activity assay; invadopodia assay Oncogene Medium 35773411

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. The Journal of cell biology 589 9832565
1995 A role for Rac in Tiam1-induced membrane ruffling and invasion. Nature 507 7753201
1997 Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science (New York, N.Y.) 394 9367959
2005 Par-3 controls tight junction assembly through the Rac exchange factor Tiam1. Nature cell biology 382 15723052
2005 PAR-6-PAR-3 mediates Cdc42-induced Rac activation through the Rac GEFs STEF/Tiam1. Nature cell biology 313 15723051
2005 The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines. Neuron 312 15721239
2002 Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. Nature 306 12075356
2002 Tiam1 mediates Ras activation of Rac by a PI(3)K-independent mechanism. Nature cell biology 267 12134164
2000 CD44 interaction with tiam1 promotes Rac1 signaling and hyaluronic acid-mediated breast tumor cell migration. The Journal of biological chemistry 241 10636882
2005 Regulation of sphingosine 1-phosphate-induced endothelial cytoskeletal rearrangement and barrier enhancement by S1P1 receptor, PI3 kinase, Tiam1/Rac1, and alpha-actinin. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 238 16195373
2010 miR-21 and miR-31 converge on TIAM1 to regulate migration and invasion of colon carcinoma cells. The Journal of biological chemistry 232 20826792
2006 The polarity protein PAR-3 and TIAM1 cooperate in dendritic spine morphogenesis. Nature cell biology 178 16474385
2002 Interaction of Rac exchange factors Tiam1 and Ras-GRF1 with a scaffold for the p38 mitogen-activated protein kinase cascade. Molecular and cellular biology 163 12024021
2007 The Rac1 guanine nucleotide exchange factor Tiam1 mediates EphB receptor-dependent dendritic spine development. Proceedings of the National Academy of Sciences of the United States of America 161 17440041
2007 The Par-Tiam1 complex controls persistent migration by stabilizing microtubule-dependent front-rear polarity. Current biology : CB 151 17825562
2001 Evidence for the involvement of Tiam1 in axon formation. The Journal of neuroscience : the official journal of the Society for Neuroscience 150 11264310
1999 Ca2+/calmodulin-dependent protein kinase II regulates Tiam1 by reversible protein phosphorylation. The Journal of biological chemistry 145 10212259
2004 The role of the guanine nucleotide exchange factor Tiam1 in cellular migration, invasion, adhesion and tumor progression. Breast cancer research and treatment 135 14999151
2006 TrkB binds and tyrosine-phosphorylates Tiam1, leading to activation of Rac1 and induction of changes in cellular morphology. Proceedings of the National Academy of Sciences of the United States of America 120 16801538
2004 The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions. The Journal of biological chemistry 110 15138270
2013 miRNA-218 inhibits osteosarcoma cell migration and invasion by down-regulating of TIAM1, MMP2 and MMP9. Asian Pacific journal of cancer prevention : APJCP 109 23886165
2000 Ankyrin-Tiam1 interaction promotes Rac1 signaling and metastatic breast tumor cell invasion and migration. The Journal of cell biology 109 10893266
1995 Oncogenic activity of Tiam1 and Rac1 in NIH3T3 cells. Oncogene 106 8570171
2015 By downregulating TIAM1 expression, microRNA-329 suppresses gastric cancer invasion and growth. Oncotarget 105 25654811
2007 HGF attenuates thrombin-induced endothelial permeability by Tiam1-mediated activation of the Rac pathway and by Tiam1/Rac-dependent inhibition of the Rho pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 103 17428964
2005 The rac activator Tiam1 is a Wnt-responsive gene that modifies intestinal tumor development. The Journal of biological chemistry 103 16249175
2012 MiR-29c suppresses invasion and metastasis by targeting TIAM1 in nasopharyngeal carcinoma. Cancer letters 98 23142282
2000 Regulation of the Rac1-specific exchange factor Tiam1 involves both phosphoinositide 3-kinase-dependent and -independent components. The Biochemical journal 97 10998360
1999 Tiam1 is involved in the regulation of bufalin-induced apoptosis in human leukemia cells. Oncogene 95 10229192
2010 miR-10b targets Tiam1: implications for Rac activation and carcinoma migration. The Journal of biological chemistry 90 20444703
2006 Tiam1 regulates cell adhesion, migration and apoptosis in colon tumor cells. Clinical & experimental metastasis 87 17086355
2005 The Rac activator Tiam1 is required for (alpha)3(beta)1-mediated laminin-5 deposition, cell spreading, and cell migration. The Journal of cell biology 86 16330714
2005 Tiam1-IRSp53 complex formation directs specificity of rac-mediated actin cytoskeleton regulation. Molecular and cellular biology 85 15899863
2004 Tiam1 mediates neurite outgrowth induced by ephrin-B1 and EphA2. The EMBO journal 83 14988728
2008 Paracingulin regulates the activity of Rac1 and RhoA GTPases by recruiting Tiam1 and GEF-H1 to epithelial junctions. Molecular biology of the cell 82 18653465
2009 The Rac activator Tiam1 controls efficient T-cell trafficking and route of transendothelial migration. Blood 81 19139083
2008 Tiam1 and Rac1 are required for platelet-activating factor-induced endothelial junctional disassembly and increase in vascular permeability. The Journal of biological chemistry 81 19095647
2006 Tiam1 takes PARt in cell polarity. Trends in cell biology 81 16650994
2014 MiR-141 suppresses the migration and invasion of HCC cells by targeting Tiam1. PloS one 80 24551096
2013 The guanine nucleotide exchange factor Tiam1: a Janus-faced molecule in cellular signaling. Cellular signalling 80 24308970
2015 An EGFR/PI3K/AKT axis promotes accumulation of the Rac1-GEF Tiam1 that is critical in EGFR-driven tumorigenesis. Oncogene 78 25746002
2009 SRC-induced disassembly of adherens junctions requires localized phosphorylation and degradation of the rac activator tiam1. Molecular cell 78 19285946
2017 TIAM1 Antagonizes TAZ/YAP Both in the Destruction Complex in the Cytoplasm and in the Nucleus to Inhibit Invasion of Intestinal Epithelial Cells. Cancer cell 77 28416184
1997 Lysophosphatidic acid induces threonine phosphorylation of Tiam1 in Swiss 3T3 fibroblasts via activation of protein kinase C. The Journal of biological chemistry 74 9407095
2014 miR-29b suppresses tumor growth and metastasis in colorectal cancer via downregulating Tiam1 expression and inhibiting epithelial-mesenchymal transition. Cell death & disease 73 25032858
1995 Sequence of the human invasion-inducing TIAM1 gene, its conservation in evolution and its expression in tumor cell lines of different tissue origin. Oncogene 73 7731688
2015 CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling. Molecular cell 71 25684205
2008 Combined analysis of Rac1, IQGAP1, Tiam1 and E-cadherin expression in gastric cancer. Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 70 18246045
2014 Phosphatidylinositol 5-phosphate regulates invasion through binding and activation of Tiam1. Nature communications 69 24905281
2004 The RacGEF Tiam1 inhibits migration and invasion of metastatic melanoma via a novel adhesive mechanism. Journal of cell science 65 15340013
2014 Tiam1/Rac1 signals contribute to the proliferation and chemoresistance, but not motility, of chronic lymphocytic leukemia cells. Blood 64 24501217
2000 Tiam1 mutations in human renal-cell carcinomas. International journal of cancer 64 11054665
2019 TIAM1 promotes chemoresistance and tumor invasiveness in colorectal cancer. Cell death & disease 63 30890693
2010 CADM1 interacts with Tiam1 and promotes invasive phenotype of human T-cell leukemia virus type I-transformed cells and adult T-cell leukemia cells. The Journal of biological chemistry 62 20215110
2012 Tiam1 interaction with the PAR complex promotes talin-mediated Rac1 activation during polarized cell migration. The Journal of cell biology 61 23071154
2019 Circular RNA circ-RAD23B promotes cell growth and invasion by miR-593-3p/CCND2 and miR-653-5p/TIAM1 pathways in non-small cell lung cancer. Biochemical and biophysical research communications 60 30722989
2022 ALKBH5 inhibits thyroid cancer progression by promoting ferroptosis through TIAM1-Nrf2/HO-1 axis. Molecular and cellular biochemistry 56 36070054
2016 The fibroblast Tiam1-osteopontin pathway modulates breast cancer invasion and metastasis. Breast cancer research : BCR 56 26821678
2014 HUWE1 ubiquitylates and degrades the RAC activator TIAM1 promoting cell-cell adhesion disassembly, migration, and invasion. Cell reports 56 25543140
2022 TIAM1-mediated synaptic plasticity underlies comorbid depression-like and ketamine antidepressant-like actions in chronic pain. The Journal of clinical investigation 55 36519542
2007 16-kDa prolactin inhibits endothelial cell migration by down-regulating the Ras-Tiam1-Rac1-Pak1 signaling pathway. Cancer research 55 18006851
2015 MicroRNA-377 suppresses cell proliferation and invasion by inhibiting TIAM1 expression in hepatocellular carcinoma. PloS one 53 25739101
2007 Tiam1 and betaPIX mediate Rac-dependent endothelial barrier protective response to oxidized phospholipids. Journal of cellular physiology 51 17219408
2013 The sirtuins promote Dishevelled-1 scaffolding of TIAM1, Rac activation and cell migration. Oncogene 50 24362520
2010 Tiam1-Rac signaling counteracts Eg5 during bipolar spindle assembly to facilitate chromosome congression. Current biology : CB 48 20346677
2016 Tiam1/Rac1 complex controls Il17a transcription and autoimmunity. Nature communications 47 27725632
2012 Tiam1, negatively regulated by miR-22, miR-183 and miR-31, is involved in migration, invasion and viability of ovarian cancer cells. Oncology reports 47 22469921
2006 Interaction between Tiam1 and the Arp2/3 complex links activation of Rac to actin polymerization. The Biochemical journal 47 16599904
2013 Prostaglandin D2-DP signaling promotes endothelial barrier function via the cAMP/PKA/Tiam1/Rac1 pathway. Arteriosclerosis, thrombosis, and vascular biology 46 23307871
2012 β2-syntrophin and Par-3 promote an apicobasal Rac activity gradient at cell-cell junctions by differentially regulating Tiam1 activity. Nature cell biology 46 23103911
2013 NMDA receptor couples Rac1-GEF Tiam1 to direct oligodendrocyte precursor cell migration. Glia 45 24123220
2010 The role of fibroblast Tiam1 in tumor cell invasion and metastasis. Oncogene 44 20802514
2006 Lentivirus-mediated silencing of Tiam1 gene influences multiple functions of a human colorectal cancer cell line. Neoplasia (New York, N.Y.) 44 17132223
2015 Tiam1-Rac1 Axis Promotes Activation of p38 MAP Kinase in the Development of Diabetic Retinopathy: Evidence for a Requisite Role for Protein Palmitoylation. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 43 25967961
2024 S-Nitrosylation of Septin2 Exacerbates Aortic Aneurysm and Dissection by Coupling the TIAM1-RAC1 Axis in Macrophages. Circulation 42 38357802
2015 Cdk1 phosphorylates the Rac activator Tiam1 to activate centrosomal Pak and promote mitotic spindle formation. Nature communications 42 26078008
2017 Tiam1 promotes thyroid carcinoma metastasis by modulating EMT via Wnt/β-catenin signaling. Experimental cell research 41 29277502
2012 Tiam1 regulates the Wnt/Dvl/Rac1 signaling pathway and the differentiation of midbrain dopaminergic neurons. Molecular and cellular biology 41 23109420
2010 The Tiam1 PDZ domain couples to Syndecan1 and promotes cell-matrix adhesion. Journal of molecular biology 41 20361982
2015 The Downregulation of MiR-182 Is Associated with the Growth and Invasion of Osteosarcoma Cells through the Regulation of TIAM1 Expression. PloS one 40 25973950
2013 EphA2 signaling following endocytosis: role of Tiam1. Traffic (Copenhagen, Denmark) 38 24112471
2013 Balanced Tiam1-rac1 and RhoA drives proliferation and invasion of pancreatic cancer cells. Molecular cancer research : MCR 37 23322732
2012 Tiam1 is associated with hepatocellular carcinoma metastasis. International journal of cancer 36 22573407
2014 5-Lipoxygenase and cysteinyl leukotriene receptor 1 regulate epidermal growth factor-induced cell migration through Tiam1 upregulation and Rac1 activation. Cancer science 32 24350867
2011 Distinct ligand specificity of the Tiam1 and Tiam2 PDZ domains. Biochemistry 32 21192692
2007 Proteomic analysis of Tiam1-mediated metastasis in colorectal cancer. Cell biology international 31 17376711
2017 Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction. Biochemical pharmacology 30 28202288
2004 Antisense Tiam1 down-regulates the invasiveness of 95D cells in vitro. Acta biochimica et biophysica Sinica 30 15295645
2022 Loss-of-function variants in TIAM1 are associated with developmental delay, intellectual disability, and seizures. American journal of human genetics 29 35240055
2022 YAP1 induces invadopodia formation by transcriptionally activating TIAM1 through enhancer in breast cancer. Oncogene 29 35773411
2020 The Rac-GEF Tiam1 Promotes Dendrite and Synapse Stabilization of Dentate Granule Cells and Restricts Hippocampal-Dependent Memory Functions. The Journal of neuroscience : the official journal of the Society for Neuroscience 29 33328293
2009 The PHCCEx domain of Tiam1/2 is a novel protein- and membrane-binding module. The EMBO journal 29 19893486
2012 Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells. Journal of cell science 28 22302986
2021 Tumor-associated mesenchymal stem cells promote hepatocellular carcinoma metastasis via a DNM3OS/KDM6B/TIAM1 axis. Cancer letters 27 33472090
2018 Competition between TIAM1 and Membranes Balances Endophilin A3 Activity in Cancer Metastasis. Developmental cell 27 29920278
2008 Tiam1-deficiency impairs mammary tumor formation in MMTV-c-neu but not in MMTV-c-myc mice. Journal of cancer research and clinical oncology 27 18592271
2019 Tiam1 is Critical for Glutamatergic Synapse Structure and Function in the Hippocampus. The Journal of neuroscience : the official journal of the Society for Neuroscience 26 31597723
2015 ApoER2 and Reelin are expressed in regenerating peripheral nerve and regulate Schwann cell migration by activating the Rac1 GEF protein, Tiam1. Molecular and cellular neurosciences 26 26386179
2007 Involvement of Tiam1 in apoptosis induced by bufalin in HeLa cells. Anticancer research 26 17352239
2016 Involvement of Tiam1, RhoG and ELMO2/ILK in Rac1-mediated phagocytosis in human trabecular meshwork cells. Experimental cell research 25 27539661

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