Affinage

IQGAP1

Ras GTPase-activating-like protein IQGAP1 · UniProt P46940

Length
1657 aa
Mass
189.3 kDa
Annotated
2026-04-28
100 papers in source corpus 43 papers cited in narrative 43 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

IQGAP1 is a large multidomain scaffold protein that integrates cytoskeletal dynamics, small GTPase signaling, and mitogen-activated kinase cascades to coordinate cell polarity, migration, proliferation, and vesicular trafficking. It directly binds and stabilizes GTP-loaded Cdc42, Rac1, RhoA/C, and Rap1 through its GRD and IQ domains, while simultaneously recruiting MAPK pathway components (B-Raf, MEK1/2, ERK1/2) and PI3K-Akt-mTOR effectors via its IQ motifs to control growth factor signal output (PMID:8670801, PMID:16135787, PMID:22328503, PMID:31235839). IQGAP1 dimerizes and directly engages actin filaments—bundling, capping barbed ends, and suppressing disassembly—while coupling to microtubule plus-ends through CLIP-170 to polarize the cytoskeleton at the leading edge, and activating N-WASP/Arp2/3-dependent actin nucleation through an autoinhibited C-terminal mechanism (PMID:34731043, PMID:12110184, PMID:17085436). Its scaffolding activity is tuned by Ca²⁺/calmodulin-dependent conformational regulation, SUMOylation at K1445, ubiquitination by HECTD1 and TRIM56, and phosphorylation at S480 (by GLK) and S1443 (by PKCα), and it additionally scaffolds receptor complexes including EGFR and insulin receptor to modulate receptor autophosphorylation and downstream Akt/ERK signaling, with loss of IQGAP1 in mice impairing cardiac stress adaptation, glucose homeostasis, AMPK activation, and hippocampal synaptic plasticity (PMID:21349850, PMID:28082684, PMID:33191271, PMID:21653857, PMID:21493702, PMID:28987385, PMID:31431460).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1996 High

    Identification of IQGAP1 as a Cdc42/Rac1 effector and calmodulin-binding protein localized to lamellipodia established the founding biochemical framework: a GTPase-regulated, IQ-domain-containing scaffold at the actin cortex.

    Evidence Affinity purification, in vitro GTPase assays, co-IP, yeast epistasis, and immunofluorescence in mammalian cells and S. cerevisiae

    PMID:8670801

    Open questions at the time
    • Mechanism of GAP-like inhibition versus stabilization of GTP-Cdc42 was ambiguous
    • In vivo phenotype of IQGAP1 loss unknown
    • Downstream effectors beyond actin not identified
  2. 2002 High

    Discovery that IQGAP1 bridges Rac1/Cdc42 to CLIP-170 at microtubule plus-ends resolved how GTPase signaling achieves cortical microtubule capture and cell polarization.

    Evidence Reciprocal co-IP, GFP live imaging, dominant-negative constructs in Vero fibroblasts

    PMID:12110184

    Open questions at the time
    • Whether IQGAP1-CLIP-170 interaction is direct or bridged was not resolved with purified proteins
    • Contribution of IQGAP1 to microtubule dynamics in vivo untested
  3. 2003 High

    Functional evidence that IQGAP1 promotes cell motility and invasion through Cdc42/Rac1 connected the scaffold to a cancer-relevant phenotype and showed it sustains active GTPase pools rather than simply acting as a GAP.

    Evidence siRNA knockdown and dominant-negative ΔGRD in invasion/migration assays with in vitro GTPase activity measurements

    PMID:12900413

    Open questions at the time
    • Mechanism by which IQGAP1 increases GTP-Cdc42 (GDI displacement vs. GEF recruitment) unresolved
    • Relative contributions of Rac1 vs. Cdc42 to IQGAP1-driven invasion unclear
  4. 2005 High

    Demonstration that IQGAP1 directly and cooperatively scaffolds MEK1/2 and ERK1/2 (and later B-Raf) established IQGAP1 as a bona fide MAPK scaffold that tunes signal amplitude rather than simply relaying it.

    Evidence In vitro binding with purified proteins, co-IP, siRNA knockdown, IQGAP1 mutant constructs, EGF stimulation in multiple studies

    PMID:14970219 PMID:16135787

    Open questions at the time
    • Stoichiometry and spatial organization of the scaffold-kinase complex unknown
    • Whether IQGAP1 scaffolding confers switch-like vs. graded ERK activation untested
  5. 2006 High

    Reconstitution of IQGAP1-stimulated N-WASP/Arp2/3-dependent actin polymerization, gated by an intramolecular autoinhibition mechanism, revealed how IQGAP1 directly nucleates branched actin independently of Cdc42.

    Evidence Kinetic actin polymerization assays with GST-tagged IQGAP1 fragments, co-IP, siRNA

    PMID:17085436

    Open questions at the time
    • In vivo relevance of the autoinhibition not demonstrated
    • How autoinhibition is relieved in cells (signal or PTM) undetermined
  6. 2007 High

    Mapping distinct binding interfaces for Rac1 vs. Cdc42 on IQGAP1's GRD, and identification of Rap1 as an additional IQ-domain GTPase partner regulated by calmodulin, expanded the GTPase repertoire and introduced Ca²⁺-dependent selectivity.

    Evidence Site-directed mutagenesis with quantitative affinity measurements (Rac1/Cdc42); in vitro binding and Rap1 activation assays

    PMID:17517894 PMID:17984089

    Open questions at the time
    • Structural basis for differential switch-II recognition unresolved
    • Functional consequence of Rap1 regulation on adhesion in vivo not established
  7. 2008 High

    Integration of Ca²⁺/calmodulin with B-Raf binding and identification of IQGAP1 in exocyst-septin-mediated secretion revealed that IQGAP1 coordinates MAPK signaling and vesicle trafficking, both modulated by Ca²⁺.

    Evidence Direct in vitro binding with Ca²⁺ manipulation for B-Raf; co-IP and pulse-chase secretion assays in β-cells for exocyst

    PMID:18216334 PMID:18567582

    Open questions at the time
    • Whether calmodulin and B-Raf compete for identical IQGAP1 residues was not mapped
    • Exocyst interaction not validated with purified proteins
  8. 2011 High

    In vivo knockout studies revealed physiological scaffold functions: IQGAP1-null mice showed impaired cardiac MAPK/AKT stress signaling, reduced hippocampal NR2A surface expression with LTP/memory deficits, and dysregulated T-cell activation, establishing organ-level requirements.

    Evidence IQGAP1 KO mice with aortic banding, hippocampal electrophysiology and behavior, and T-cell cytokine assays; co-IP in each system

    PMID:21493702 PMID:21653857 PMID:22573807

    Open questions at the time
    • Cell-type-specific conditional KO phenotypes not dissected
    • Whether cardiac and neuronal phenotypes are ERK-dependent or involve other scaffolded pathways unclear
  9. 2011 High

    Direct binding to EGFR and identification of PKCα-mediated S1443 phosphorylation showed that IQGAP1 amplifies receptor tyrosine kinase autophosphorylation via a calmodulin-sensitive, phosphorylation-gated mechanism.

    Evidence In vitro binding, MS phosphosite identification, siRNA and IQGAP1-null cell reconstitution, PKC inhibitors

    PMID:21349850

    Open questions at the time
    • Whether S1443 phosphorylation directly modulates EGFR affinity not determined
    • Generalizability to other RTKs beyond EGFR and IR not tested at this point
  10. 2013 High

    A WW-domain-derived peptide disrupting IQGAP1-ERK interaction inhibited RAS/RAF-driven tumorigenesis in vivo, providing pharmacologic proof that the scaffold function is essential for oncogenic RAS signaling and is therapeutically targetable.

    Evidence Peptide competition, IQGAP1 KO/knockdown in mouse tumor models, systemic peptide delivery

    PMID:23603816

    Open questions at the time
    • Later work showed the IQ domain, not WW, is the primary ERK-binding site (PMID:28396345), raising questions about peptide mechanism of action
    • Pharmacokinetics and off-target effects of WW peptide not fully addressed
  11. 2017 High

    Quantitative reconstitution redefined the ERK/MEK binding site to the IQ domain (Kd ~8 µM) rather than WW, while identification of S480 phosphorylation by GLK, SUMOylation at K1445, and HECTD1-mediated ubiquitination revealed a multilayered PTM code controlling IQGAP1 stability and signaling output.

    Evidence Quantitative in vitro binding (IQ vs. WW), kinase assays, SUMOylation mapping, ubiquitination assays, KO/knockdown rescue experiments

    PMID:28073378 PMID:28396345 PMID:28987385 PMID:31431460

    Open questions at the time
    • How SUMOylation and ubiquitination at distinct lysines are coordinated is unknown
    • Whether IQ3-dependent PI3K scaffolding and IQ-dependent ERK scaffolding are mutually exclusive on a single dimer not tested
  12. 2017 High

    Direct binding to insulin receptor and IRS-1 with impaired glucose homeostasis in IQGAP1-null mice established IQGAP1 as a metabolic scaffold, paralleled by its role in AMPK/CaMKK2 complex formation and fasting gene regulation.

    Evidence In vitro binding, domain mapping, IQGAP1 KO mice with glucose tolerance tests and AMPK phosphorylation rescue

    PMID:28082684 PMID:33191271

    Open questions at the time
    • Tissue-specific contributions (hepatic vs. skeletal muscle vs. adipose) to metabolic phenotype not resolved
    • Whether AMPK and insulin receptor scaffolding occur on the same or separate IQGAP1 pools unknown
  13. 2021 High

    Single-molecule reconstitution demonstrated that IQGAP1 dimers bundle actin filaments, transiently cap barbed ends, and suppress disassembly through domain-specific and dimerization-dependent activities, providing a direct biophysical mechanism for cytoskeletal regulation.

    Evidence Single-molecule TIRF microscopy with domain deletion and dimerization-deficient mutants

    PMID:34731043

    Open questions at the time
    • How barbed-end capping is relieved in vivo (e.g., by calmodulin or GTPase binding) not shown
    • Actin bundling geometry and filament spacing not structurally resolved
  14. 2022 Medium

    IQGAP1 was identified as an adaptor bridging GSDMD to ESCRT-Tsg101 for exosomal packaging of GSDMD and IL-1β, linking inflammasome effector export to CDC42-dependent IQGAP1 activation.

    Evidence Proteomic identification, co-IP, exosome isolation, siRNA knockdown with NLRP3 inflammasome stimulation

    PMID:36373462

    Open questions at the time
    • Direct binding between IQGAP1 and GSDMD not shown with purified proteins
    • Generalizability beyond LPS/macrophage context untested
    • Whether IQGAP1 is required for all GSDMD exosomal export or only a subset unclear

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length atomic structure of IQGAP1 (free and in complex with key partners), the rules governing competitive or cooperative binding of its >90 reported partners, and the in vivo consequences of individual domain disruptions in tissue-specific conditional knockouts remain unresolved.
  • No high-resolution structure of full-length IQGAP1 or its dimer
  • How the cell resolves competition among dozens of IQ-domain ligands (calmodulin, ERK, EGFR, AMPK, YAP, ER) is unknown
  • Conditional tissue-specific KO phenotypes largely unexplored

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 11 GO:0098772 molecular function regulator activity 6 GO:0008092 cytoskeletal protein binding 5
Localization
GO:0005886 plasma membrane 5 GO:0005856 cytoskeleton 4 GO:0005829 cytosol 3 GO:0031410 cytoplasmic vesicle 3 GO:0005768 endosome 1
Pathway
R-HSA-162582 Signal Transduction 12 R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-1643685 Disease 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2 R-HSA-1640170 Cell Cycle 2
Partners
BRAFCDC42CLIP1EGFRMAP2K1MAPK1PRKAA1RAC1
Complex memberships
Exocyst-septin-IQGAP1 complexIQGAP1-CLIP-170-Cdc42/Rac1 cortical capture complexIQGAP1-MEK-ERK MAPK scaffold

Evidence

Reading pass · 43 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 IQGAP1 binds to and inhibits the GTPase activity of Cdc42 and Rac1 (but not Ras) through its GRD domain, localizes to lamellipodia where it co-localizes with actin, and binds calmodulin via its IQ domain; expression of GRD fragment inhibits the CDC24/CDC42 pathway in yeast. Affinity chromatography purification, in vitro GTPase activity assay, co-immunoprecipitation, yeast genetic epistasis, immunofluorescence The EMBO journal High 8670801
2002 IQGAP1 interacts directly with CLIP-170 at the growing ends of microtubules; activated Rac1/Cdc42 form a tripartite complex with IQGAP1 and CLIP-170 to capture microtubules at the cortical leading edge, establishing a polarized microtubule array and cell polarization. Co-immunoprecipitation, GFP live imaging, dominant-negative and deletion constructs, Vero fibroblast expression studies Cell High 12110184
2003 IQGAP1 promotes cell motility and invasion in a Cdc42- and Rac1-dependent manner; it increases the amount of active Cdc42 in vitro and in cells; dominant-negative IQGAP1ΔGRD attenuates invasion driven by constitutively active Cdc42. siRNA knockdown, dominant-negative construct overexpression, in vitro GTPase activity assay, migration/invasion assays The Journal of biological chemistry High 12900413
2004 IQGAP1 directly binds ERK2 (demonstrated with pure proteins), and manipulation of IQGAP1 levels significantly reduces growth factor-stimulated ERK1/2 activity; the ERK2-binding region of IQGAP1 is required for this modulation. In vitro binding with purified proteins, co-immunoprecipitation from cell lysates, siRNA knockdown, IQGAP1 deletion mutants The Journal of biological chemistry High 14970219
2005 IQGAP1 functions as a molecular scaffold for the MAPK pathway by directly binding MEK1 and MEK2 as well as ERK2; MEK-ERK binding to IQGAP1 is cooperative and both knockdown and overexpression of IQGAP1 reduce EGF-stimulated MEK and ERK activation. In vitro binding assays, co-immunoprecipitation, siRNA knockdown, IQGAP1 mutant constructs, EGF stimulation assays Molecular and cellular biology High 16135787
2006 The C-terminal half of IQGAP1 activates N-WASP by interacting with its BR-CRIB domain in a Cdc42-like manner to stimulate Arp2/3-dependent actin assembly; the N-terminal half of IQGAP1 autoinhibits this activation by associating with the C-terminal region. Pull-down experiments with GST-tagged fragments, kinetic actin polymerization assays, co-immunoprecipitation, siRNA knockdown, quantitative co-localization analysis The Journal of biological chemistry High 17085436
2007 IQGAP1 directly binds the small GTPase Rap1; interaction is enhanced by GTP-loading of Rap1 and is eliminated by calmodulin; Rap1 binds to the IQ region of IQGAP1; overexpression of IQGAP1 attenuates adhesion- and cAMP-mediated Rap1 activation. In vitro binding with pure proteins, co-immunoprecipitation, confocal microscopy, point mutants of IQGAP1, Rap1 activation assays The Journal of biological chemistry High 17517894
2007 IQGAP1-stimulated cell migration requires direct interaction with actin; Ca2+/calmodulin binding to IQGAP1 negatively regulates its pro-migratory function; Cdc42 localization at the leading edge is not required for maximal IQGAP1-driven migration. IQGAP1 point mutant constructs, calmodulin inhibitory peptide, confocal microscopy, migration assays Cellular signalling Medium 17544257
2007 The IQGAP1-Rac1 and IQGAP1-Cdc42 binding interfaces differ: switch II mutations abolish Rac1 binding but not Cdc42 binding; switch I residues 32 and 36 are important for both; the Rho insert loop does not contribute to IQGAP1 binding. Site-directed mutagenesis of Rac1/Cdc42, quantitative affinity measurements, competition assays The Journal of biological chemistry High 17984089
2008 IQGAP1 integrates Ca2+/calmodulin with B-Raf signaling: Ca2+ promotes direct IQGAP1-B-Raf binding, which is inhibited by calmodulin in a Ca2+-dependent manner; chelation of intracellular Ca2+ enhances EGF-stimulated B-Raf activity in an IQGAP1-dependent manner. In vitro binding with pure proteins, co-immunoprecipitation, Ca2+ ionophore/chelator treatments, B-Raf activity assays The Journal of biological chemistry High 18567582
2008 IQGAP1 associates and co-localizes with the exocyst-septin complex; CDC42 activation abolishes this association and inhibits secretion; the N-terminus of IQGAP1 binds the exocyst-septin complex and enhances secretion, while the C-terminus (binding CDC42) inhibits secretion. Co-immunoprecipitation, co-localization, pulse-chase secretion assays, dominant-negative constructs in pancreatic beta-cells Journal of cell science Medium 18216334
2009 IQGAP1 regulates cell proliferation through a CDC42-mTOR pathway; the N-terminus of IQGAP1 interacts with mTOR, which is required for IQGAP1-mediated cell proliferation; IQGAP1 requires phosphorylation and CDC42 binding for this activity. Deletion constructs, co-immunoprecipitation, cell size measurement, transformation/migration assays Journal of cell science Medium 19454477
2010 S100P, a Ca2+-binding protein, directly and Ca2+-dependently binds IQGAP1 primarily through the IQ domain (K_D ~0.2 µM), and S100P overexpression reduces EGF-induced IQGAP1 tyrosine phosphorylation and attenuates B-Raf binding to IQGAP1 and downstream MEK1/2 activation. Affinity approach with S100P dimer, pull-down, co-immunoprecipitation, kinase activation assays, S100P mutants The Journal of biological chemistry High 21177863
2011 IQGAP1 directly binds EGFR through the IQ and kinase domains respectively; calmodulin disrupts this interaction; EGF induces IQGAP1 Ser1443 phosphorylation via PKCα; loss of IQGAP1 severely attenuates EGF-stimulated EGFR autophosphorylation, which is rescued by wild-type IQGAP1 reconstitution. Co-immunoprecipitation, in vitro binding with pure proteins, MS-based phosphorylation assay, siRNA, IQGAP1 null cells reconstitution, PKC inhibitors The Journal of biological chemistry High 21349850
2011 CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology of neurons by coordinating microtubule-actin cytoskeleton interaction; mTOR kinase interacts with CLIP-170 and is needed for efficient CLIP-170/IQGAP1 complex formation; dynamic microtubules, CLIP-170, and IQGAP1 are required for PI3K-mTOR-induced increases in dendritic arbor complexity. Knockdown in rat neurons, live imaging, co-immunoprecipitation, dendritic arbor morphometry The Journal of neuroscience Medium 21430156
2011 IQGAP1 is a component of NMDAR multiprotein complexes and functionally interacts with NR2A subunits and ERK1/2; IQGAP1 knockout mice show decreased surface NR2A expression and impaired ERK signaling upon NR2A-dependent NMDAR stimulation, accompanied by reduced hippocampal dendritic spine density and long-term memory deficits. IQGAP1 knockout mice, co-immunoprecipitation, surface biotinylation, hippocampal LTP recordings The Journal of neuroscience High 21653857
2011 IQGAP1 scaffolds c-Raf, MEK1/2, ERK1/2, and AKT in the heart; IQGAP1-null mice show impaired delayed (4-day) but not acute (10-min) MEK/ERK and AKT phosphorylation after pressure overload, leading to accelerated maladaptive cardiac remodeling. IQGAP1-null mice, aortic banding model, pull-down assays, phosphorylation time-course analysis Cardiovascular research High 21493702
2011 IQGAP1 acts as a dual negative regulator in T cells: it limits TCR-mediated signaling (LCK activation, IL-2/IFN-γ production) and F-actin assembly dynamics via distinct IQGAP1 domain-dependent mechanisms. IQGAP1-null T cells, siRNA in Jurkat cells, IQGAP1 domain constructs, F-actin imaging, cytokine measurement Journal of immunology Medium 22573807
2012 IQGAP1 acts upstream of RhoA/C (regulating their GTP loading) and downstream of RhoA/C (mediating their effects on proliferation/migration); it interacts directly with GTP-bound, prenylated RhoA and RhoC but not RhoB. Proteomics screen, co-immunoprecipitation, GTP-loading measurements in constitutively active mutants, siRNA knockdown, adenoviral constructs The Journal of biological chemistry Medium 22992742
2012 IQGAP1 conserved role in regulating TORC1: yeast two-hybrid identified Tco89p (TORC1-specific subunit) as an Iqg1p partner; mammalian IQGAP1 binds mTORC1 and Akt1 and modulates the mTORC1-S6K1→Akt1 negative feedback loop. Yeast two-hybrid, complementary yeast and mammalian experiments, co-immunoprecipitation, kinase activity assays Journal of cell science Medium 22328503
2013 Activated Cdc42 bound to IQGAP1 recruits GDP-bound Rab27a to the plasma membrane to regulate endocytosis of insulin secretory membranes; IQGAP1 silencing inhibits endocytosis and glucose-induced redistribution of Rab27a and coronin 3. Identification of IQGAP1 as Rab27a-interacting protein, co-immunoprecipitation, silencing, dominant-negative IQGAP1, endocytosis assays Molecular and cellular biology Medium 24100016
2013 IQGAP1 binds TGF-β receptor II (TβRII) and promotes SMURF1-mediated ubiquitination and degradation of TβRII, thereby suppressing TGF-β-dependent myofibroblast differentiation; IQGAP1 knockdown stabilizes TβRII and potentiates TGF-β1 signaling. Co-immunoprecipitation, IQGAP1 knockdown in hepatic stellate cells, ubiquitination assay, in vivo tumor implantation The Journal of clinical investigation High 23454766
2013 The IQGAP1 WW domain peptide disrupts IQGAP1-ERK1/2 interactions and inhibits RAS/RAF-driven tumorigenesis; IQGAP1 is required for RAS-driven tumorigenesis in mouse and human tissue. WW domain peptide competition, IQGAP1 knockout/knockdown in mouse models, tumor growth assays, systemic peptide delivery Nature medicine High 23603816
2013 IQGAP1 regulates nuclear localization of β-catenin via importin-β5 in Wnt signaling; IQGAP1 depletion in Xenopus embryos reduces Wnt-induced nuclear β-catenin accumulation and Wnt target gene expression; Ran1 GTPase also contributes. Xenopus embryo depletion, co-immunoprecipitation, nuclear fractionation, Wnt target gene expression assays The Journal of biological chemistry Medium 24196961
2014 IQGAP1 interacts with LGR4 and DVL following RSPO stimulation to bring RSPO-LGR4 to the Wnt signaling complex; this promotes MEK1/2-mediated phosphorylation of LRP5/6 and potentiates both canonical and non-canonical Wnt signaling. Yeast two-hybrid/proteomics identification, co-immunoprecipitation, IQGAP1 siRNA, luciferase Wnt reporter assay, kinase assays Proceedings of the National Academy of Sciences Medium 24639526
2014 IQGAP1 directly binds ERα and ERβ; interaction is mediated by the IQ domain of IQGAP1 and the hinge region of ERα; knockdown of IQGAP1 attenuates estradiol-induced transcription of estrogen-responsive genes (pS2, progesterone receptor, cyclin D1). In vitro binding with pure proteins, co-immunoprecipitation, domain mapping constructs, siRNA knockdown, transcription assays The Journal of biological chemistry High 24550401
2014 IQGAP1 forms a complex with Asef (a Rac/Cdc42 GEF) following HGF stimulation, mediated by the C-terminal domain of IQGAP1; this complex localizes to the cell cortex and promotes Rac activation, leading to IQGAP1 interaction with Arp3 and cortactin to enhance endothelial barrier function. Co-immunoprecipitation, siRNA knockdown, domain-mapping constructs, Rac activation assays, transendothelial resistance measurement The Journal of biological chemistry Medium 25492863
2014 IQGAP1 acts as a scaffold that colocalizes p190A-RhoGAP with RhoA to inactivate RhoA and suppress airway smooth muscle contraction; IQGAP1 knockout mice have enhanced RhoA activity and increased airway hyperresponsiveness. IQGAP1 knockout mice, co-immunoprecipitation, proximity ligation assay, RhoA activity assays, tracheal ring contraction force measurement, primary human airway smooth muscle cell knockdown The Journal of clinical investigation High 25271629
2015 IQGAP1 directly promotes CXCR4 cell surface expression and recycling via EEA-1+ endosomes; IQGAP1 depletion disrupts CXCR4 trafficking to late endosomes, reduces surface CXCR4, and blocks SDF-1-induced ERK activation and cell migration; upon SDF-1 treatment IQGAP1 binds α-tubulin and localizes to CXCR4-containing endosomes. siRNA knockdown, forced overexpression, endosomal fractionation, co-immunoprecipitation, confocal imaging, migration assays The Journal of cell biology Medium 26195666
2015 The IQ3 motif of IQGAP1 specifically scaffolds PI3K-Akt pathway components (PIPKIα, PI3K); deletion or blocking of IQ3 reduces Akt activation without affecting ERK or EGFR binding to IQGAP1. IQ3 deletion mutant, IQ3 peptide inhibitor, co-immunoprecipitation, Akt/ERK activation assays, cell migration/invasion assays Scientific reports Medium 31235839
2016 IQGAP1 directly binds YAP via its IQ domain (interacting with the TEAD-binding domain of YAP); IQGAP1 knockout or knockdown increases nuclear YAP-TEAD complex formation and YAP-TEAD-mediated transcription. Co-immunoprecipitation, in vitro binding with pure proteins, domain mapping, CRISPR/Cas9 IQGAP1 knockout, transcription reporter assays The Journal of biological chemistry High 27440047
2017 AKT-phosphorylated FOXO1 (at Ser319) binds IQGAP1 and impedes IQGAP1-dependent ERK1/2 phosphorylation; decreased FOXO1 increases pERK1/2 in cancer cells; a FOXO1-derived phospho-mimicking peptide reverses IQGAP1-mediated ERK activation. Co-immunoprecipitation, FOXO1 phospho-mutants, IQGAP1 interaction assays, ERK phosphorylation assays, in vivo mouse experiments The EMBO journal High 28279977
2017 SUMO1 SUMOylates IQGAP1 at K1445, stabilizing IQGAP1 by reducing ubiquitination; IQGAP1 SUMOylation activates ERK, MEK, and AKT phosphorylation; K1445 mutation reduces CRC cell growth, migration, and tumor formation. SUMO modification mapping, K1445 mutant, ubiquitination assay, ERK/MEK/AKT phosphorylation assays, in vitro and xenograft models Cancer letters Medium 28987385
2017 The IQ domain of IQGAP1 (not the WW domain) is both necessary and sufficient for binding ERK1/2 and MEK1/2; WW domain peptides contribute little binding energy to ERK-IQGAP1 interaction; ERK2-IQGAP1 binding does not require ERK2 phosphorylation and the Kd is ~8 µM. Quantitative in vitro binding assays, IQ and WW domain deletion constructs, phospho-ERK2 and kinase-dead ERK2 variants The Journal of biological chemistry High 28396345
2017 IQGAP1 associates with NLRC3 and disrupts the NLRC3-STING interaction; IQGAP1 knockdown phenocopies NLRC3 deficiency by increasing IFN-β production in response to cytosolic nucleic acids. Yeast two-hybrid identification, co-immunoprecipitation, siRNA knockdown in THP1 and HeLa cells, IFN-β ELISA Journal of immunology Medium 28864474
2017 IQGAP1 directly binds both insulin receptor (IR) via its IQ region and IRS-1 via the IRS-1 phosphotyrosine-binding domain interacting with the IQGAP1 C-terminal tail; loss of IQGAP1 reduces insulin-stimulated Akt and ERK phosphorylation and impairs glucose homeostasis in vivo. In vitro binding with pure proteins, co-immunoprecipitation, domain mapping, IQGAP1 knockout mice, in vivo glucose tolerance The Journal of biological chemistry High 28082684
2017 HECTD1 (E3 ubiquitin ligase) interacts with IQGAP1 and regulates its degradation through ubiquitination; loss of HECTD1 increases IQGAP1 levels, accelerating cell spreading and impairing directional migration; IQGAP1 overexpression phenocopies HECTD1 loss, and IQGAP1 knockdown rescues HECTD1-null migration defects. HECTD1 mutant MEFs, co-immunoprecipitation, ubiquitination assay, siRNA rescue experiments, cell migration analysis Cell communication and signaling Medium 28073378
2019 GLK/MAP4K3 directly phosphorylates IQGAP1 at Ser-480 via interaction of GLK proline-rich regions with the IQGAP1 WW domain; this phosphorylation enhances Cdc42 activation and subsequent cell migration and lung cancer metastasis; IQGAP1 depletion abolishes GLK-induced migration. In vitro kinase assay, co-immunoprecipitation, domain mapping, phospho-specific assay, IQGAP1 knockdown in migration and metastasis models, GLK transgenic mice Cancer research High 31431460
2019 CD13 tethers the IQGAP1-ARF6-EFA6 complex to the plasma membrane to promote ARF6 GTPase activation and β1 integrin recycling during cell migration; phosphorylated CD13, IQGAP1, GTP-bound ARF6, and EFA6 form a complex at the leading edge. Co-immunoprecipitation, mass spectrometry, ARF6 activation assays, β1 integrin trafficking assays, migration assays, siRNA knockdown Science signaling Medium 31040262
2020 IQGAP1 binds directly to the α1 subunit of AMPK and to CaMKK2 via its IQ domain; IQGAP1 is required for maximum AMPK activation by metformin and Ca2+; IQGAP1-null mice show impaired gluconeogenesis and fatty acid synthesis gene regulation in fasting. In vitro binding with fusion proteins, co-immunoprecipitation, siRNA knockdown, IQGAP1-null mice, AMPK phosphorylation rescue experiments The Journal of biological chemistry High 33191271
2021 Full-length IQGAP1 forms dimers that stably bind actin filament sides and transiently cap barbed ends; these interactions bundle filaments, suppress barbed end growth, and inhibit filament disassembly; each activity depends on distinct combinations of IQGAP1 domains and/or dimerization. Single-molecule TIRF microscopy, single-filament imaging, domain deletion constructs, dimerization mutants Molecular biology of the cell High 34731043
2022 IQGAP1 functions as an adaptor bridging GSDMD to the ESCRT component Tsg101 to promote packaging of GSDMD and IL-1β into exosomes; this process requires LPS-induced GTP-bound CDC42 activation of IQGAP1 and is identified through non-biased proteomics. Proteomic identification, co-immunoprecipitation, exosome isolation, siRNA knockdown, CDC42 activation assays, NLRP3 inflammasome stimulation The EMBO journal Medium 36373462
2023 TRIM56 promotes K48-to-K63-linked poly-ubiquitination transition of IQGAP1 at Lys-1230 by interacting with IQGAP1, which in turn promotes CDC42 activation and glioma cell migration and invasion. Co-immunoprecipitation, ubiquitination assay, site-directed mutagenesis (K1230), CDC42 activation assay, in vitro and in vivo migration models Cell death & disease Medium 36870986

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Rac1 and Cdc42 capture microtubules through IQGAP1 and CLIP-170. Cell 502 12110184
1996 IQGAP1, a calmodulin-binding protein with a rasGAP-related domain, is a potential effector for cdc42Hs. The EMBO journal 342 8670801
2005 IQGAP1: a key regulator of adhesion and migration. Journal of cell science 304 15890984
2005 IQGAP1 is a scaffold for mitogen-activated protein kinase signaling. Molecular and cellular biology 213 16135787
1990 [Sar1]angiotensin II receptor-mediated stimulation of protein synthesis in chick heart cells. The American journal of physiology 211 1690518
2004 IQGAP1 binds ERK2 and modulates its activity. The Journal of biological chemistry 189 14970219
2003 IQGAP1 promotes cell motility and invasion. The Journal of biological chemistry 180 12900413
2000 A dominant negative mutant of sar1 GTPase inhibits protein transport from the endoplasmic reticulum to the Golgi apparatus in tobacco and Arabidopsis cultured cells. The Plant journal : for cell and molecular biology 164 10972878
2013 IQGAP1 scaffold-kinase interaction blockade selectively targets RAS-MAP kinase-driven tumors. Nature medicine 162 23603816
2006 IQGAP1 stimulates actin assembly through the N-WASP-Arp2/3 pathway. The Journal of biological chemistry 125 17085436
2007 IQGAP1 stimulates proliferation and enhances tumorigenesis of human breast epithelial cells. The Journal of biological chemistry 116 17981797
2003 IQGAP1 as signal integrator: Ca2+, calmodulin, Cdc42 and the cytoskeleton. FEBS letters 115 12729888
2017 AKT-phosphorylated FOXO1 suppresses ERK activation and chemoresistance by disrupting IQGAP1-MAPK interaction. The EMBO journal 104 28279977
2014 RSPO-LGR4 functions via IQGAP1 to potentiate Wnt signaling. Proceedings of the National Academy of Sciences of the United States of America 95 24639526
2011 CLIP-170 and IQGAP1 cooperatively regulate dendrite morphology. The Journal of neuroscience : the official journal of the Society for Neuroscience 83 21430156
2011 IQGAP1 regulates NR2A signaling, spine density, and cognitive processes. The Journal of neuroscience : the official journal of the Society for Neuroscience 82 21653857
2008 A dual role for IQGAP1 in regulating exocytosis. Journal of cell science 82 18216334
2011 MAPK scaffold IQGAP1 binds the EGF receptor and modulates its activation. The Journal of biological chemistry 80 21349850
2013 IQGAP1 suppresses TβRII-mediated myofibroblastic activation and metastatic growth in liver. The Journal of clinical investigation 79 23454766
2023 IQGAP1 promotes mitochondrial damage and activation of the mtDNA sensor cGAS-STING pathway to induce endothelial cell pyroptosis leading to atherosclerosis. International immunopharmacology 76 37597406
2011 IQGAP1 regulates ERK1/2 and AKT signalling in the heart and sustains functional remodelling upon pressure overload. Cardiovascular research 75 21493702
2012 The Pseudomonas aeruginosa N-acylhomoserine lactone quorum sensing molecules target IQGAP1 and modulate epithelial cell migration. PLoS pathogens 73 23071436
2009 IQGAP1 regulates cell proliferation through a novel CDC42-mTOR pathway. Journal of cell science 70 19454477
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
2010 IQGAP1 is overexpressed in hepatocellular carcinoma and promotes cell proliferation by Akt activation. Experimental & molecular medicine 67 20530982
2004 The role of ADP-ribosylation factor and SAR1 in vesicular trafficking in plants. Biochimica et biophysica acta 67 15238254
2016 MALAT1 promotes the proliferation and invasion of thyroid cancer cells via regulating the expression of IQGAP1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 65 27470543
2008 Plant Sar1 isoforms with near-identical protein sequences exhibit different localisations and effects on secretion. Plant molecular biology 61 18322804
2007 IQGAP1 binds Rap1 and modulates its activity. The Journal of biological chemistry 60 17517894
2020 IQGAP1 promotes anoikis resistance and metastasis through Rac1-dependent ROS accumulation and activation of Src/FAK signalling in hepatocellular carcinoma. British journal of cancer 59 32632148
2013 Silencing of mammalian Sar1 isoforms reveals COPII-independent protein sorting and transport. Traffic (Copenhagen, Denmark) 55 23433038
2012 Rho isoform-specific interaction with IQGAP1 promotes breast cancer cell proliferation and migration. The Journal of biological chemistry 55 22992742
2007 The IQGAP1-Rac1 and IQGAP1-Cdc42 interactions: interfaces differ between the complexes. The Journal of biological chemistry 55 17984089
2019 IQGAP1 promotes pancreatic cancer progression and epithelial-mesenchymal transition (EMT) through Wnt/β-catenin signaling. Scientific reports 54 31101875
2013 Small GTPase Sar1 is crucial for proglutelin and α-globulin export from the endoplasmic reticulum in rice endosperm. Journal of experimental botany 53 23682119
1997 The SAR1 gene of Arabidopsis acts downstream of the AXR1 gene in auxin response. Development (Cambridge, England) 50 9108374
2017 Regulation of the Sar1 GTPase Cycle Is Necessary for Large Cargo Secretion from the Endoplasmic Reticulum. Frontiers in cell and developmental biology 48 28879181
2012 A conserved role of IQGAP1 in regulating TOR complex 1. Journal of cell science 47 22328503
2010 Rap1b facilitates NK cell functions via IQGAP1-mediated signalosomes. The Journal of experimental medicine 45 20733035
2008 IQGAP1 integrates Ca2+/calmodulin and B-Raf signaling. The Journal of biological chemistry 45 18567582
2019 MAP4K3/GLK Promotes Lung Cancer Metastasis by Phosphorylating and Activating IQGAP1. Cancer research 44 31431460
2013 IQGAP1 protein regulates nuclear localization of β-catenin via importin-β5 protein in Wnt signaling. The Journal of biological chemistry 44 24196961
2017 SUMOylation of IQGAP1 promotes the development of colorectal cancer. Cancer letters 42 28987385
2010 S100P is a novel interaction partner and regulator of IQGAP1. The Journal of biological chemistry 42 21177863
2015 Inter-kingdom Signaling by the Legionella Quorum Sensing Molecule LAI-1 Modulates Cell Migration through an IQGAP1-Cdc42-ARHGEF9-Dependent Pathway. PLoS pathogens 41 26633832
2021 Role of IQGAP1 in Carcinogenesis. Cancers 39 34439095
2012 The cytoskeletal adaptor protein IQGAP1 regulates TCR-mediated signaling and filamentous actin dynamics. Journal of immunology (Baltimore, Md. : 1950) 39 22573807
2019 CD13 tethers the IQGAP1-ARF6-EFA6 complex to the plasma membrane to promote ARF6 activation, β1 integrin recycling, and cell migration. Science signaling 38 31040262
2016 IQGAP1 Binds to Yes-associated Protein (YAP) and Modulates Its Transcriptional Activity. The Journal of biological chemistry 38 27440047
2015 IQGAP1 is a phosphoinositide effector and kinase scaffold. Advances in biological regulation 38 26554303
2014 Hepatocyte growth factor-induced Asef-IQGAP1 complex controls cytoskeletal remodeling and endothelial barrier. The Journal of biological chemistry 38 25492863
1998 Activities of mutant Sar1 proteins in guanine nucleotide binding, GTP hydrolysis, and cell-free transport from the endoplasmic reticulum to the Golgi apparatus. Journal of biochemistry 34 9756629
2019 The Specificity of EGF-Stimulated IQGAP1 Scaffold Towards the PI3K-Akt Pathway is Defined by the IQ3 motif. Scientific reports 33 31235839
2015 miR-506 regulates breast cancer cell metastasis by targeting IQGAP1. International journal of oncology 33 26398880
2014 IQGAP1 binds to estrogen receptor-α and modulates its function. The Journal of biological chemistry 33 24550401
2013 A PAK6-IQGAP1 complex promotes disassembly of cell-cell adhesions. Cellular and molecular life sciences : CMLS 32 24352566
2007 Multiple proteins mediate IQGAP1-stimulated cell migration. Cellular signalling 32 17544257
2003 Identification of an IQGAP1/AKAP79 complex in beta-cells. Journal of cellular biochemistry 32 12938160
2022 The Ras GTPase-activating-like protein IQGAP1 bridges Gasdermin D to the ESCRT system to promote IL-1β release via exosomes. The EMBO journal 30 36373462
2014 Overexpression of DNAJB6 promotes colorectal cancer cell invasion through an IQGAP1/ERK-dependent signaling pathway. Molecular carcinogenesis 30 25044025
2013 Overexpression of IQGAP1 in human pancreatic cancer. Hepatobiliary & pancreatic diseases international : HBPD INT 30 24103286
2012 IQGAP1 interacts with components of the slit diaphragm complex in podocytes and is involved in podocyte migration and permeability in vitro. PloS one 30 22662192
2010 An emerging role for IQGAP1 in regulating protein traffic. TheScientificWorldJournal 30 20495773
2015 IQGAP1 and IQGAP3 Serve Individually Essential Roles in Normal Epidermal Homeostasis and Tumor Progression. The Journal of investigative dermatology 29 25848980
2018 Regulation of extracellular matrix degradation and metastatic spread by IQGAP1 through endothelin-1 receptor signalling in ovarian cancer. Matrix biology : journal of the International Society for Matrix Biology 28 30367951
2013 Activated Cdc42-bound IQGAP1 determines the cellular endocytic site. Molecular and cellular biology 28 24100016
2012 IQGAP1 regulates hyaluronan-mediated fibroblast motility and proliferation. Cellular signalling 28 22634185
2022 Acinetobacter baumannii Outer Membrane Protein A Induces Pulmonary Epithelial Barrier Dysfunction and Bacterial Translocation Through The TLR2/IQGAP1 Axis. Frontiers in immunology 27 35844614
2021 The interplay between IQGAP1 and small GTPases in cancer metastasis. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 26 33434854
2005 The receptor protein-tyrosine phosphatase PTPmu interacts with IQGAP1. The Journal of biological chemistry 26 16380380
2011 IQGAP1 involvement in MTOC and granule polarization in NK-cell cytotoxicity. European journal of immunology 25 21681737
2005 Expression pattern of the scaffold protein IQGAP1 in lung cancer. Oncology reports 25 15706411
2023 Integrin β4 promotes DNA damage-related drug resistance in triple-negative breast cancer via TNFAIP2/IQGAP1/RAC1. eLife 24 37787041
2021 MIB1 upregulates IQGAP1 and promotes pancreatic cancer progression by inducing ST7 degradation. Molecular oncology 24 33793053
2018 The lincRNA MIRAT binds to IQGAP1 and modulates the MAPK pathway in NRAS mutant melanoma. Scientific reports 24 30026510
2011 IQGAP1 is a novel CXCR2-interacting protein and essential component of the "chemosynapse". PloS one 24 21876773
2021 Single-molecule imaging of IQGAP1 regulating actin filament dynamics. Molecular biology of the cell 23 34731043
2016 An emerging role for IQGAP1 in tight junction control. Small GTPases 23 27880081
2011 RhoC protein stimulates migration of gastric cancer cells through interaction with scaffold protein IQGAP1. Molecular medicine reports 23 21537845
2023 ASAP1 activates the IQGAP1/CDC42 pathway to promote tumor progression and chemotherapy resistance in gastric cancer. Cell death & disease 22 36792578
2017 HECTD1 controls the protein level of IQGAP1 to regulate the dynamics of adhesive structures. Cell communication and signaling : CCS 22 28073378
2017 The Scaffolding Protein IQGAP1 Interacts with NLRC3 and Inhibits Type I IFN Production. Journal of immunology (Baltimore, Md. : 1950) 22 28864474
2024 Cancer-associated fibroblasts regulate mitochondrial metabolism and inhibit chemosensitivity via ANGPTL4-IQGAP1 axis in prostate cancer. Journal of advanced research 21 39647634
2023 Overexpressed ZC3H13 suppresses papillary thyroid carcinoma growth through m6A modification-mediated IQGAP1 degradation. Journal of the Formosan Medical Association = Taiwan yi zhi 21 36739231
2021 CircRNA circ-IQGAP1 Knockdown Alleviates Interleukin-1β-Induced Osteoarthritis Progression via Targeting miR-671-5p/TCF4. Orthopaedic surgery 21 33675175
2021 MAL2 interacts with IQGAP1 to promote pancreatic cancer progression by increasing ERK1/2 phosphorylation. Biochemical and biophysical research communications 21 33780861
2017 New model for the interaction of IQGAP1 with CDC42 and RAC1. Small GTPases 21 28622072
2011 Salmonella enterica serotype Typhimurium usurps the scaffold protein IQGAP1 to manipulate Rac1 and MAPK signalling. The Biochemical journal 21 21851337
2015 IQGAP1 promotes CXCR4 chemokine receptor function and trafficking via EEA-1+ endosomes. The Journal of cell biology 20 26195666
2014 Differential expression of IQGAP1/2 in Hepatocellular carcinoma and its relationship with clinical outcomes. Asian Pacific journal of cancer prevention : APJCP 20 24998570
2016 IQGAP1 gene silencing induces apoptosis and decreases the invasive capacity of human hepatocellular carcinoma cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 19 27488117
2023 TRIM56 acts through the IQGAP1-CDC42 signaling axis to promote glioma cell migration and invasion. Cell death & disease 18 36870986
2017 Absence of IQGAP1 Protein Leads to Insulin Resistance. The Journal of biological chemistry 18 28082684
2017 Knockdown of IQGAP1 inhibits proliferation and epithelial-mesenchymal transition by Wnt/β-catenin pathway in thyroid cancer. OncoTargets and therapy 18 28352188
2017 The WW domain of the scaffolding protein IQGAP1 is neither necessary nor sufficient for binding to the MAPKs ERK1 and ERK2. The Journal of biological chemistry 18 28396345
2014 IQGAP1-dependent scaffold suppresses RhoA and inhibits airway smooth muscle contraction. The Journal of clinical investigation 18 25271629
2022 Targeting ARF1-IQGAP1 interaction to suppress colorectal cancer metastasis and vemurafenib resistance. Journal of advanced research 17 36396045
2020 IQGAP1 binds AMPK and is required for maximum AMPK activation. The Journal of biological chemistry 17 33191271
2013 ARF1 and SAR1 GTPases in endomembrane trafficking in plants. International journal of molecular sciences 17 24013371
2005 Roles of IQGAP1 in cell polarization and migration. Novartis Foundation symposium 17 16355537