Affinage

GIT1

ARF GTPase-activating protein GIT1 · UniProt Q9Y2X7

Length
761 aa
Mass
84.3 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/8 claims corpus-supported (88%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

GIT1 is a multidomain ARF GTPase-activating scaffold protein that integrates signaling at focal adhesions, synapses, and endosomes to control receptor trafficking, cytoskeletal dynamics, and cell migration (PMID:9826657, PMID:11896197). Through its N-terminal ARF-GAP domain it acts on ARF6 to negatively regulate clathrin-dependent GPCR internalization, receptor recycling, and regulated exocytosis (PMID:9826657, PMID:10655494, PMID:15775968, PMID:16439353). Its Spa2-homology (SHD) and coiled-coil domains form binding platforms for FAK, MEK1/ERK1/2, PLCγ, and CaMKII, coupling growth-factor and GPCR inputs to sustained ERK activation, PLCγ activation, and Rac1/Cdc42 signaling (PMID:10938112, PMID:14523024, PMID:14701758, PMID:17562871); GIT1 also activates PAK directly through its ARF-GAP domain independent of GAP catalysis or GTPase binding (PMID:15082779). Its C-terminal paxillin-binding (FAT-like four-helix) domain targets a GIT1/βPIX/PAK module to adhesions and the leading edge, where the domains assemble a dimeric GIT1–trimeric βPIX heteropentameric complex to drive adhesion turnover, protrusion, and migration (PMID:16717130, PMID:17467235, PMID:19136011); engagement of this domain is gated by an intramolecular inhibitory mechanism involving tyrosines 246/293 and by phosphorylation at Ser46 (PKD3), Ser709 (PAK), and Tyr321 (Src) (PMID:16797488, PMID:22302306, PMID:22893698, PMID:24699139). At synapses, GIT1 nucleates a GIT1/βPIX/Rac1/PAK complex that governs dendritic spine and synapse formation, AMPA receptor clustering via liprin-α, GABA-A receptor surface stability, and mTOR-dependent local protein synthesis, with GluN3A-containing NMDARs acting as a negative regulator of complex assembly (PMID:12629171, PMID:15800193, PMID:24297929, PMID:25284783, PMID:34787081). GIT1 tyrosine phosphorylation is written by Src and erased by PTPζ (PMID:11381105, PMID:15923189). Loss of GIT1 in mice shifts the excitation/inhibition balance and produces ADHD-like and memory phenotypes, and rare loss-of-function GIT1 variants impairing PAK3/MAPK activation are found in schizophrenia (PMID:21499268, PMID:27457813, PMID:35505090). Beyond neuronal and adhesion roles, GIT1 contributes to endosomal EGFR degradation via sorting nexin 6, autophagy via Beclin1, microtubule nucleation at centrosomes, eNOS activation, MAT2B-dependent Ras/Raf/MEK/ERK signaling in cancer, and suppression of Notch ICD nuclear translocation (PMID:18523162, PMID:27012601, PMID:24764294, PMID:23325601, PMID:30546041, PMID:35318302).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1998 High

    Established GIT1's founding biochemical identity as an ARF-GAP and linked that catalytic activity to control of GPCR signaling, answering what enzymatic function the protein carries.

    Evidence Overexpression with GAP-dead mutants and ARF GAP/receptor internalization assays

    PMID:9826657

    Open questions at the time
    • Which ARF isoform(s) are physiological substrates was not resolved here
    • Endogenous regulation of GAP activity not addressed
  2. 2000 High

    Defined GIT1 as an adhesion adaptor by mapping direct binding to paxillin and FAK and showing it disassembles focal complexes to drive motility, establishing its scaffolding role at adhesions.

    Evidence Deletion-mutant co-IP and motility assays in fibroblasts/epithelial cells; receptor internalization comparison across GPCR endocytic routes

    PMID:10655494 PMID:10938112

    Open questions at the time
    • Structural basis of paxillin binding not yet determined
    • How PIX regulates focal complex disassembly mechanistically unclear
  3. 2001 High

    Identified PTPζ as a phosphatase acting on tyrosine-phosphorylated GIT1 in neurons, opening the question of how phosphorylation tunes GIT1 function.

    Evidence Yeast substrate-trap, in vitro dephosphorylation, co-IP and immunohistochemistry

    PMID:11381105

    Open questions at the time
    • Specific GIT1 tyrosines targeted not mapped
    • Functional consequence of dephosphorylation not established
  4. 2002 High

    Resolved how GIT1 distributes among adhesions, leading edge, and cytoplasmic complexes by domain mapping, and showed PAK interaction is required for its migration-promoting activity.

    Evidence Live-cell imaging, deletion mutants, migration/protrusion assays; co-IP during S1P-induced FA remodeling

    PMID:11896197 PMID:12482769

    Open questions at the time
    • Trigger for compartment cycling not defined
    • Domain-level mechanism of the S1P-associated complex not established
  5. 2003 High

    Extended GIT1 into the nervous system, showing synaptic targeting controls spine/synapse number through Rac and links GIT1 to AMPA receptor clustering via liprin-α.

    Evidence Dominant-negative and Rac epistasis in hippocampal neurons, PSD fractionation, EM, co-IP

    PMID:12629171 PMID:12695502

    Open questions at the time
    • Identity of the synaptic localization domain receptor/anchor unresolved
    • How GIT1-liprin-α selectively controls AMPAR trafficking not mechanistically detailed
  6. 2004 High

    Showed GIT1 scaffolds MEK1-ERK and PLCγ signaling as a Src substrate and activates PAK via its ARF-GAP domain independent of catalysis, defining its role as a signaling integrator beyond GAP activity.

    Evidence Domain-mapping co-IP, knockdown, ERK/PLCγ activation and in vitro kinase assays; huntingtin co-IP and aggregation; thrombin/RhoA antisense studies

    PMID:14523024 PMID:14701758 PMID:15016733 PMID:15082779 PMID:15383276

    Open questions at the time
    • Structural basis for catalysis-independent PAK activation unclear
    • Physiological relevance of huntingtin recruitment limited to disease tissue
  7. 2005 High

    Placed GIT1 at the center of a PIX/Rac/PAK module driving spine formation and at focal adhesions recruiting ERK, while connecting its GAP activity to receptor recycling, defining converging adhesion, synaptic, and trafficking circuits.

    Evidence RNAi with epistasis rescue, FRET for Rac, siRNA, SYF cells, recycling assays

    PMID:15775968 PMID:15800193 PMID:15923189

    Open questions at the time
    • How a single scaffold partitions among these circuits in vivo not addressed
    • Direct Rac GEF coupling to local activation not fully resolved
  8. 2006 High

    Established phospho-regulation of the GIT1-paxillin axis (paxillin S273 and GIT1 S709 by PAK) as a positive-feedback loop for migration, and confirmed GAP-dependent control of ARF6 exocytosis, clarifying how the adhesion module is dynamically tuned.

    Evidence Phosphomutant epistasis, in vitro kinase assays, real-time single-cell exocytosis, βPIX-driven redistribution studies

    PMID:16439353 PMID:16717130 PMID:16787945 PMID:16797488

    Open questions at the time
    • Kinetics of the feedback loop in vivo not measured
    • How βPIX dimerization controls GIT1 endosomal localization mechanistically unclear
  9. 2007 High

    Provided structural and autoregulatory understanding: the paxillin-binding domain is a FAT-like four-helix bundle binding paxillin LD motifs, and an intramolecular N-/C-terminal interaction keeps GIT1 binding-incompetent until released.

    Evidence Crystallography, deletion-mutant reconstitution, co-IP; ephrinB/Grb4-Tyr392 and PAK-PIX-GIT1 complex disruption in vivo

    PMID:17310244 PMID:17429073 PMID:17467235 PMID:17898078

    Open questions at the time
    • What physiological signal releases the intramolecular clamp not defined
    • Tyrosine phosphorylation shown not to regulate paxillin binding leaves its functional target open
  10. 2008 High

    Defined the GIT1/βPIX heteropentameric architecture by crystallography and extended GIT1 into endosomal EGFR degradation (SNX6), transcriptional control via CaMKII-HDAC5, and Drosophila muscle morphogenesis, broadening its mechanistic and developmental scope.

    Evidence X-ray structures and ultracentrifugation, NMR of PBD, co-IP/domain mapping, siRNA, Drosophila genetics

    PMID:18292392 PMID:18448431 PMID:18523162 PMID:18996366 PMID:19136011

    Open questions at the time
    • Functional role of the unoccupied βPIX binding site unknown
    • In vivo relevance of CaMKII-HDAC5 axis not established
  11. 2009 Medium

    Showed receptor tyrosine kinase inputs (EphA2-Nck1, Rac3) converge on GIT1 to modulate ARF6 and adhesion/cell-cell contacts, and identified MYO18A linkage, refining how upstream signals route through the GIT1 complex.

    Evidence Co-IP, ARF6 activity assays, siRNA/dominant-negative, proteomics with functional rescue

    PMID:19193766 PMID:19494130 PMID:19923322

    Open questions at the time
    • Single-lab biochemical pathways without reciprocal in vivo validation
    • How GIT1 simultaneously serves Rac1/Rac3-distinct routes unclear
  12. 2011 High

    Demonstrated organismal consequences of GIT1 loss, with knockout mice showing reduced Rac1 signaling, shifted excitation/inhibition balance, and ADHD-like phenotypes reversible by stimulants, establishing GIT1 as a neurodevelopmental disease-relevant gene.

    Evidence GIT1 knockout mice, behavior, EEG, electrophysiology, pharmacological rescue

    PMID:21499268

    Open questions at the time
    • Cell-type-specific contributions not dissected here
    • Molecular link from Rac1 deficit to E/I imbalance incomplete
  13. 2012 High

    Identified new phospho-writers (PKD3 at Ser46, Src-dependent Tyr321 for FAK binding) and a GIT1-eNOS partnership, refining how site-specific phosphorylation directs GIT1 localization and effector coupling.

    Evidence MS phosphosite ID, phosphomutants, kinase/phosphatase inhibitors, co-IP, NO measurement

    PMID:22294688 PMID:22302306 PMID:22893698

    Open questions at the time
    • Integration of multiple phosphosites into a unified regulatory code not addressed
    • eNOS interaction validated in single system
  14. 2013 High

    Revealed an oncogenic GIT1 scaffold function in which MAT2B-GIT1 recruits Raf/MEK/ERK and stabilizes Ras to drive liver cancer growth, and refined the intramolecular tyrosine clamp (Y246/Y293).

    Evidence Recombinant pulldown, co-IP, siRNA, orthotopic liver cancer model; site-directed mutagenesis and migration assays

    PMID:23325601 PMID:24699139

    Open questions at the time
    • Whether MAT2B-GIT1 scaffold operates outside liver cancer not addressed
    • Physiological trigger releasing the Y246/Y293 clamp unresolved
  15. 2014 High

    Connected GIT1 phosphorylation to eNOS activation downstream of ETB/Akt/Src, and established GIT1/βPIX/Rac1/PAK control of GABA-A receptor surface stability and inhibitory synaptic strength.

    Evidence Phospho-mutants, inhibitors, co-IP, NO assays; RNAi/dominant-negative with GABAAR imaging and electrophysiology

    PMID:24764294 PMID:25284783

    Open questions at the time
    • How GIT1 balances excitatory and inhibitory receptor regulation simultaneously unclear
    • In vivo eNOS pathway validation lacking
  16. 2016 High

    Uncovered noncanonical GIT1 complexes—a Raptor/Rictor-independent mTOR complex supporting astrocyte survival and a GIT1/βPIX/PAK1 module regulating centrosomal microtubule nucleation—plus schizophrenia-associated loss-of-function variants, expanding GIT1 mechanism beyond adhesion/synapse scaffolding.

    Evidence MS of mTOR complex, co-IP, knockdown, AKT inhibitors; microtubule regrowth, in vitro kinase, γ-tubulin pulldown; variant functional assays in neurons

    PMID:27012601 PMID:27340174 PMID:27457813

    Open questions at the time
    • Composition and regulation of the noncanonical GIT1-mTOR complex incompletely defined
    • Disease causality of variants beyond cell-based assays not established
  17. 2018 Medium

    Linked GIT1 to autophagy by showing it interacts with Beclin1 and promotes its Thr119 phosphorylation to disrupt Beclin1-Bcl2 and activate osteoclast autophagy, adding a degradative-pathway role.

    Evidence GIT1 KO mice, co-IP, Beclin1 phosphorylation assays, autophagosome quantification, fracture repair model

    PMID:30546041

    Open questions at the time
    • Kinase responsible for Beclin1 Thr119 phosphorylation not identified
    • Generality beyond osteoclasts untested
  18. 2019 Medium

    Showed GIT1 enhances NEMO affinity for K63-ubiquitin chains to activate NF-κB and downstream Notch-driven VEGF secretion, defining a GIT1 role in inflammatory/angiogenic signaling.

    Evidence Co-IP, shRNA, NF-κB/Notch reporters, nuclear fractionation, GIT1 KO mice

    PMID:31502302

    Open questions at the time
    • Direct structural basis of GIT1-NEMO CC2 interaction not resolved
    • Single-lab pathway without reciprocal validation
  19. 2021 High

    Defined a GIT1-mTOR-Raptor neuronal complex coupling synaptic stimuli to local protein synthesis and memory consolidation, gated negatively by GluN3A, integrating GIT1 into activity-dependent translation.

    Evidence Co-IP, GluN3A conditional KO mice, siRNA, mTOR activity, polysome profiling, behavioral memory tasks

    PMID:34787081

    Open questions at the time
    • Reconciliation with the earlier Raptor/Rictor-independent GIT1-mTOR complex not addressed
    • How GluN3A binding mechanistically blocks mTOR recruitment unclear
  20. 2022 High

    Established brain-specific roles in memory and spine density through phospho-proteomic networks of disease risk genes, and identified GIT1 as a suppressor of Notch ICD nuclear transport in breast cancer, consolidating its neurological and oncogenic functions.

    Evidence Conditional neural GIT1 KO, behavior, spine analysis, phospho-proteomics; co-IP, knockdown/overexpression, Notch reporter, nuclear fractionation, xenograft

    PMID:35318302 PMID:35505090

    Open questions at the time
    • Direct substrate relationships within the GIT1 phospho-network not all causally validated
    • Mechanism by which GIT1 retains Notch ICD in the cytoplasm not structurally defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How a single scaffold's distinct complexes (adhesion GIT1/βPIX/PAK, synaptic Rac/mTOR, oncogenic MAT2B-Raf, NEMO, Beclin1, centrosomal γ-tubulin) are selected and coordinated in a given cell, and which signals release the intramolecular autoinhibition in vivo, remain unresolved.
  • No unified model of context-dependent complex selection
  • In vivo triggers of conformational activation undefined
  • Quantitative stoichiometry of competing complexes unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0098772 molecular function regulator activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005768 endosome 3 GO:0005829 cytosol 3 GO:0005634 nucleus 1 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-112316 Neuronal System 4 R-HSA-5653656 Vesicle-mediated transport 4 R-HSA-1266738 Developmental Biology 2 R-HSA-9612973 Autophagy 1
Partners
ARHGEF7LIPRIN-ALPHAMAP2K1MTORPAK1PLCG1PTK2PXN
Complex memberships
GIT1-mTOR/Raptor neuronal complexGIT1/βPIX heteropentamerGIT1/βPIX/PAK moduleMAT2B-GIT1-Raf/MEK/ERK scaffold

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 GIT1 is a GTPase-activating protein (GAP) for the ADP ribosylation factor (ARF) family of small GTP-binding proteins. Overexpression of GIT1 reduces beta2-adrenergic receptor signaling and increases receptor phosphorylation by reducing receptor internalization and resensitization; these effects require intact ARF GAP activity and do not reflect regulation of GRK kinase activity. Overexpression in cells, ARF GAP activity assays, receptor internalization and signaling assays Proceedings of the National Academy of Sciences of the United States of America High 9826657
2000 GIT1 directly interacts with paxillin via a C-terminal 125-residue domain and with focal adhesion kinase (FAK) via a conserved Spa2 homology domain (SHD). Overexpression of GIT1 causes loss of paxillin from focal complexes and stimulates cell motility; focal complex disassembly by GIT1 is regulated by PIX and is independent of actin-myosin contractile events. Overexpression in fibroblasts/epithelial cells, deletion mutant analysis, co-immunoprecipitation, cell motility assays Molecular and cellular biology High 10938112
2000 GIT1 overexpression specifically regulates internalization of GPCRs that use the clathrin-coated pit pathway in a beta-arrestin- and dynamin-sensitive manner, but does not affect receptors using other endocytic routes or constitutive (agonist-independent) internalization such as transferrin uptake. Overexpression studies, receptor internalization assays across multiple GPCR subtypes, transferrin uptake assay Proceedings of the National Academy of Sciences of the United States of America High 10655494
2001 GIT1/Cat-1 is a substrate of protein tyrosine phosphatase zeta (PTPzeta/RPTPbeta). Tyrosine-phosphorylated GIT1 binds to the substrate-trap mutant PTPzeta-D1902A and is dephosphorylated by PTPzeta in vitro. GIT1 and PTPzeta co-localize in hippocampal and neocortical neurons, and pleiotrophin (a PTPzeta ligand) increases GIT1 tyrosine phosphorylation. Yeast substrate-trapping system, in vitro dephosphorylation assay, co-immunoprecipitation in mammalian cells, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 11381105
2002 GIT1 cycles between at least three distinct subcellular compartments: adhesion-like structures, the leading edge, and cytoplasmic complexes containing paxillin, PAK, and PIX. The paxillin-binding domain (C-terminal ~140 residues) targets GIT1 to adhesions and the leading edge; the central region (ankyrin repeats + PIX-binding domain) targets GIT1 to cytoplasmic complexes. Expression of GIT1 or its C-terminal fragment increases migration rate and protrusion size/number; co-expression with kinase-dead PAK inhibits these effects, indicating PAK interaction is required. Live-cell imaging, deletion mutant expression, cell migration and protrusion assays, co-localization studies Journal of cell science High 11896197
2002 GIT1 associates with paxillin and undergoes transient association with the GIT2-paxillin complex during sphingosine 1-phosphate (S1P)-induced focal adhesion remodeling in pulmonary endothelial cells, correlating with redistribution to the cell cortical area and Rac-dependent barrier enhancement. Co-immunoprecipitation, immunofluorescence, S1P stimulation in HUVECs Journal of applied physiology Medium 12482769
2003 GIT1 is enriched at both pre- and postsynaptic terminals in cultured hippocampal neurons, targeted by a novel synaptic localization domain. Disruption of synaptic localization by a dominant-negative mutant causes mislocalization of GIT1 and its binding partner PIX, resulting in numerous dendritic protrusions and decreased synapse number; constitutively active Rac phenocopies the GIT1 mutant, while dominant-negative Rac rescues dendritic protrusion formation. Dominant-negative expression, immunofluorescence in hippocampal neurons, Rac epistasis experiments The Journal of cell biology High 12695502
2003 Liprin-alpha directly interacts with GIT1. GIT1 is enriched in postsynaptic density fractions and forms a complex with liprin-alpha, GRIP, and AMPA receptors in brain. Expression of dominant-negative constructs that disrupt the GIT1-liprin-alpha interaction causes selective reduction in dendritic and surface clustering of AMPA receptors in cultured neurons. Co-immunoprecipitation, electron microscopy, dominant-negative expression, immunofluorescence The Journal of neuroscience High 12629171
2003 GIT1 is a substrate for c-Src and undergoes tyrosine phosphorylation in response to angiotensin II and EGF. GIT1 constitutively associates with PLCgamma via PLCgamma SH2 and SH3 domains; this interaction is required for PLCgamma activation (tyrosine phosphorylation and calcium mobilization). The GIT1 Spa homology domain (SHD) and coiled-coil domain mediate PLCgamma binding, and the SHD is required for AngII- and EGF-mediated PLCgamma activation. Co-immunoprecipitation, antisense knockdown, deletion mutant analysis, calcium mobilization assay, inositol phosphate formation assay The Journal of biological chemistry High 14523024
2004 GIT1 serves as a scaffold for MEK1-ERK1/2 activation in vascular smooth muscle cells. GIT1 is a c-Src substrate that associates with MEK1 via its coiled-coil domains and SHD. GIT1-MEK1 binding is required for sustained ERK1/2 activation in response to angiotensin II and EGF. Co-immunoprecipitation, deletion mutant analysis, ERK1/2 activation assays, GIT1 overexpression/knockdown Molecular and cellular biology High 14701758
2004 GIT1 enhances huntingtin aggregation by recruiting huntingtin into membranous vesicles. GIT1 and huntingtin associate in mammalian cells under physiological conditions by co-immunoprecipitation. GIT1 localizes to neuronal inclusions and is selectively cleaved in HD brains. Yeast two-hybrid, co-immunoprecipitation, immunofluorescence in mammalian cells and HD brain tissue Molecular cell Medium 15383276
2004 GIT1 activates PAK (alphaPAK autophosphorylation) through a mechanism that requires the GIT1 N-terminal Arf-GAP domain but not its GAP catalytic activity, and does not involve Cdc42 or Rac1 GTPase binding to PAK. This PAK activation involves phosphorylation at residues common to Cdc42-mediated activation. Structure-function analysis with deletion mutants, in vitro kinase/autophosphorylation assays, co-expression studies Molecular and cellular biology High 15082779
2004 GIT1 is recruited to focal adhesions by thrombin in endothelial cells in a RhoA- and Rho kinase-dependent manner, where it co-localizes with FAK and vinculin. GIT1 undergoes Rho kinase- and Src-dependent tyrosine phosphorylation. Depletion of GIT1 by antisense oligonucleotides increases thrombin-induced cell rounding, FA formation, FAK phosphorylation, and endothelial hyperpermeability, identifying GIT1 as a negative feedback regulator of cell contraction. Antisense knockdown, dominant-negative RhoA adenoviral transfection, immunofluorescence, permeability assays Circulation research Medium 15016733
2005 A GIT1/PIX/Rac/PAK signaling module regulates dendritic spine and synapse formation. GIT1 knockdown by RNAi reduces spine and synapse formation. Rac is locally activated in dendritic spines via PIX (a Rac GEF). PAK1 and PAK3 are downstream effectors of Rac; active PAK promotes spine/synapse formation via phosphorylation of myosin II regulatory light chain (MLC). Both activated PAK and activated MLC rescue GIT1 knockdown defects, placing PAK and MLC downstream of GIT1. RNAi knockdown, FRET for Rac activation, dominant-active/negative constructs, epistasis by rescue, myosin ATPase inhibition The Journal of neuroscience High 15800193
2005 GIT1 co-localizes with ERK1/2 in focal adhesions; Src-dependent tyrosine phosphorylation of GIT1 is required for GIT1-ERK1/2 co-localization in focal adhesions. GIT1 siRNA significantly inhibits ERK1/2 recruitment to and activation in focal adhesions, as well as EGF-stimulated cell spreading and migration. Immunofluorescence, siRNA knockdown, co-localization in SYF-/- cells with Src inhibitor PP2, cell spreading/migration assays The Journal of biological chemistry High 15923189
2005 TSHR recycling relies on the hScrib-betaPIX-GIT1-ARF6 pathway. GIT1 activity (via ARF6 GAP function) and the hScrib-betaPIX interaction regulate thyrotropin receptor recycling to the plasma membrane. ARF6 is activated during TSH stimulation and plays a key role in TSHR recycling. Dominant-negative constructs, siRNA knockdown, receptor recycling/signaling assays in HEK293 and FRTL-5 cells The EMBO journal Medium 15775968
2006 Phosphorylation of paxillin serine 273 by PAK increases paxillin-GIT1 binding and promotes localization of the GIT1-PIX-PAK signaling module near the leading edge, driving adhesion turnover, protrusion, and cell migration in a positive-feedback loop. Mutants that interfere with the ternary GIT1-PIX-PAK module abolish these effects. Phosphomimetic/phospho-deficient paxillin mutants, fluorescence microscopy, adhesion turnover assays, migration assays The Journal of cell biology High 16717130
2006 GIT1 negatively regulates ARF6-dependent neuroendocrine exocytosis via its ARF GAP activity. Wild-type GIT1 overexpression inhibits growth hormone secretion from PC12 cells and reduces exocytotic events in chromaffin cells; a GIT1 mutant impaired in ARF-GAP activity loses this inhibitory effect. GIT1 is cytosolic at rest and is recruited to the plasma membrane upon cell stimulation, co-localizing with ARF6 at granule docking sites. RNAi knockdown of GIT1 increases exocytotic activity. Overexpression of WT vs. GAP-dead mutant, growth hormone secretion assay, real-time exocytosis assay in single chromaffin cells, microinjection, RNAi knockdown, immunofluorescence The Journal of biological chemistry High 16439353
2006 betaPIX controls the subcellular distribution of GIT1; overexpression of betaPIX induces accumulation of GIT1 at large perinuclear structures including the transferrin-receptor-positive endocytic compartment. Both betaPIX dimerization and a functional SH3 domain are required for this GIT1 redistribution. Disruption prevents lamellipodium formation and inhibits cell motility and neurite outgrowth. Overexpression of betaPIX mutants, immunohistochemistry, immunoelectron microscopy, time-lapse analysis, neurite outgrowth assays Journal of cell science Medium 16787945
2006 PAK phosphorylates GIT1 on serine 709, which is located in the paxillin-binding domain. Phosphorylation at S709 increases GIT1 binding to paxillin and is necessary for GIT1-induced effects on cellular protrusions. In vitro kinase assay, phosphomimetic/phospho-deficient GIT1 mutants, co-immunoprecipitation, protrusion assays Biochemical and biophysical research communications High 16797488
2007 The GIT1 C-terminal paxillin-binding domain (PBD) folds into an anti-parallel four-helix domain structurally similar to the focal adhesion targeting (FAT) domain of FAK. GIT1 PBD binds paxillin through the LD4 motif (and also LD2 motif). Tyrosine phosphorylation of the GIT1 FAH domain does not regulate paxillin binding. Crystal structure determination, mutational analysis, binding assays, structural comparison with FAK FAT domain Cellular signalling High 17467235
2007 GIT1 contains an intramolecular inhibitory mechanism: the N-terminal and C-terminal portions of GIT1 interact with each other, keeping GIT1 in a binding-incompetent state. Release of these intramolecular interactions enhances binding to paxillin and liprin-alpha. betaPIX association alone is insufficient to release the intramolecular interaction, but a PAK1 fragment including the betaPIX-binding domain enhances paxillin binding to betaPIX/GIT1 in a kinase-independent manner. Deletion mutant binding assays, co-immunoprecipitation, cell spreading assays, domain fragment reconstitution Molecular biology of the cell Medium 17898078
2007 Reverse signaling by ephrinBs controls spine morphogenesis via Grb4 and GIT1. Grb4 binds by its SH2 domain to phosphorylated Tyr392 in the synaptic localization domain of GIT1. Phosphorylation of GIT1 Tyr392 and its synaptic recruitment are regulated by ephrinB activation. Disruption of this pathway impairs spine morphogenesis and synapse formation in hippocampal neurons. Co-immunoprecipitation, phosphorylation assays, dominant-negative constructs, hippocampal neuron culture spine morphology analysis Nature neuroscience High 17310244
2007 The PAK-PIX-GIT1 complex is required for ERK-dependent myosin light chain phosphorylation and vascular permeability. Disruption of the PAK-PIX-GIT1 complex (by multiple methods including a cell-permeant peptide blocking PAK-PIX binding) inhibits LPS-induced vascular permeability in vitro and fluid leak in a mouse lung injury model. Cell-permeant peptide disruption of complex, dominant-negative constructs, ERK activation assays, mouse lung injury model Molecular biology of the cell High 17429073
2007 PLCgamma1 associates with the GIT1/beta-Pix complex via its specific array region (gammaSA); GIT1 and beta-Pix form tight complexes independently of PLCgamma1. Association with the GIT1/beta-Pix complex is required for PLCgamma1 phosphorylation and for activation of Cdc42 and Rac1, leading to integrin-mediated cell spreading. siRNA depletion of GIT1 inhibits cell spreading and Cdc42/Rac1 activation. Co-immunoprecipitation, gammaSA domain mutations, siRNA knockdown, Cdc42/Rac1 activation assays, cell spreading assays Molecular and cellular biology High 17562871
2008 Crystal structures reveal that GIT1 forms a dimeric parallel coiled-coil (CC) domain (1.4 Å resolution) and beta-PIX forms a trimeric parallel CC. Dimeric GIT1 and trimeric beta-PIX form an unusual heteropentameric complex in which each GIT1 SHD binds one GBD of beta-PIX, leaving one GBD unoccupied. Deletion of CC domains interferes with correct subcellular localization and GEF activity of PIX. X-ray crystallography, hydrodynamic studies (analytical ultracentrifugation/gel filtration), deletion mutant functional studies Journal of molecular biology High 19136011
2008 GIT1 mediates HDAC5 phosphorylation at Ser498 in response to angiotensin II via a Src-PLCgamma-CamKII-HDAC5 pathway. GIT1 constitutively associates with CamKII, and this association increases with AngII stimulation. The ARF-GAP and coiled-coil domains of GIT1 mediate CamKII binding. GIT1 knockdown decreases HDAC5 phosphorylation and reduces MEF2 transcriptional activity. Co-immunoprecipitation, siRNA knockdown, phosphorylation assays, MEF2 reporter gene assay, domain deletion analysis Arteriosclerosis, thrombosis, and vascular biology Medium 18292392
2008 GIT1 interacts with sorting nexin 6 (SNX6) via its second coiled-coil domain (CC2, aa 424-474) in endosomes; this interaction increases 3-fold after EGF treatment. Knockdown of GIT1 decreases EGF-induced EGFR degradation. Co-expression of GIT1 and SNX6 together (but not individually) decreases EGFR levels; this effect requires the GIT1 CC2 domain mediating the GIT1-SNX6 interaction. Co-immunoprecipitation, subcellular fractionation, confocal microscopy, siRNA knockdown, domain deletion (CC2-deleted GIT1), EGFR degradation assays FASEB journal High 18523162
2008 GIT1 paxillin-binding domain (PBD) solution structure determined by NMR is a four-helix bundle similar to FAT and vinculin tail domains. GIT1 PBD binds both paxillin LD2 and LD4 motifs competitively at the same surface. Paxillin Ser272 phosphorylation does not influence GIT1 PBD binding in vitro. NMR structure determination, binding assays with paxillin LD2/LD4 peptides, phosphopeptide binding assay The Journal of biological chemistry High 18448431
2008 In the Drosophila ortholog (dGIT), dGIT localizes to the termini of growing myotubes and muscle attachment sites. dGIT mutant embryos show muscle morphogenesis and myotube guidance defects, and fail to localize dPak to muscle termini. dGIT and dPak form a complex in the presence of dPIX. Drosophila genetics (dgit mutants), immunofluorescence, co-immunoprecipitation Developmental biology Medium 18996366
2009 EphA2, upon ligand activation, binds via its phosphorylated Tyr594 to the SH2 domain of Nck1, which then binds via its SH3 domain to the synaptic localizing domain of GIT1, suppressing ARF6 activity to promote cell compaction and polarization and enhance E-cadherin-based cell-cell contacts. Co-immunoprecipitation, ARF6 activity assays, dominant-negative and siRNA experiments, cell density/calcium-dependent assays Molecular biology of the cell Medium 19193766
2009 Rac3-GIT1 interaction occurs independently of betaPIX (unlike Rac1-GIT1 interaction). Rac3 expression attenuates the GIT1-paxillin interaction and disrupts focal adhesion formation. Rac3-mediated signaling requires the Arf6-GAP activity of GIT1, as Arf6 activity is strongly reduced in Rac3-expressing cells and wild-type Arf6 or the Arf6-GEF ARNO rescues cell spreading. Co-immunoprecipitation, siRNA, expression of constitutively active Arf6/ARNO, Arf6 activity assays, cell spreading assays Journal of cell science Medium 19494130
2009 MYO18A is a novel binding partner of PAK2 that binds through the betaPIX/GIT1 complex. MYO18A knockdown does not prevent PAK2/betaPIX/GIT1 complex formation but relocates the complex to focal adhesions and decreases cell motility. Proteomic approach (co-IP/MS), siRNA knockdown, in vitro binding assay, immunofluorescence, migration assays Molecular biology of the cell Medium 19923322
2011 Git1-deficient mice show decreased RAC1 signaling and inhibitory presynaptic input, and shift the neuronal excitation-inhibition balance toward excitation, leading to ADHD-like phenotypes (hyperactivity, enhanced EEG theta rhythms, impaired learning/memory) that are reversed by amphetamine and methylphenidate. GIT1 knockout mouse, behavioral assays, EEG, RAC1 signaling assays, electrophysiology for E/I balance Nature medicine High 21499268
2012 GIT1 is a novel eNOS interactor; GIT1 interacts with eNOS in the endothelial cell cytoplasm. This association is linked to stimulatory eNOS phosphorylation (Ser1177), enzyme activation, and NO synthesis. GIT1 knockdown reduces eNOS activity and NO production. Co-immunoprecipitation, siRNA knockdown, eNOS activity assays, NO measurement The Journal of biological chemistry Medium 22294688
2012 PDGF stimulates GIT1 tyrosine phosphorylation in osteoblasts and increases GIT1-FAK association at focal adhesions. The SHD of GIT1 is required for FAK binding. Phosphorylation of GIT1 tyrosine 321 (within the SHD) is critical for FAK association and for FAK activation in focal adhesions; GIT1-Y321F mutant inhibits PDGF-induced osteoblastic cell migration. Src inhibitor (PP2) and FAK siRNA, co-immunoprecipitation, GIT1 Y321F mutant, immunofluorescence, migration assays Molecular and cellular biochemistry Medium 22302306
2012 PKD3 directly phosphorylates GIT1 on serine 46, identifying GIT1 as the first specific substrate for PKD3. GIT1-S46D (phosphomimetic) localizes to motile paxillin-positive cytoplasmic complexes, while GIT1-S46A (phospho-deficient) is enriched in focal adhesions. PKD3-mediated GIT1 phosphorylation regulates paxillin trafficking and cellular protrusive activity. siRNA of PKD3, phosphosite identification by mass spectrometry, phosphomimetic/phospho-deficient GIT1 mutants, immunofluorescence, protrusion assays The Journal of biological chemistry High 22893698
2013 MAT2B variants (V1 and V2) interact directly with GIT1 and together form a scaffold that recruits MEK1, B-Raf, c-Raf, and ERK2 to activate the Ras/Raf/MEK/ERK pathway, promoting cell growth. MAT2B (but not GIT1) directly interacts with Ras, increases Ras protein stability, and promotes B-Raf/c-Raf heterodimerization; c-Raf is the key MEK1/2 activator in this complex. Co-immunoprecipitation, pull-down with recombinant and in vitro translated proteins, siRNA, overexpression, confocal microscopy, orthotopic liver cancer model Hepatology High 23325601
2013 GIT1 is enriched at dendritic spines where it binds GluN3A-containing NMDARs. GluN3A binding limits synaptic GIT1 localization and its ability to complex betaPIX, leading to decreased Rac1 activation and reduced spine density/size. GluN3A knockout favors GIT1/betaPIX complex formation and increases Rac1/PAK activation. GluN3A-GIT1 binding is regulated by synaptic activity. Co-immunoprecipitation, GluN3A knockout mouse, siRNA, dominant-negative constructs, Rac1 activity assays, spine morphology analysis Proceedings of the National Academy of Sciences of the United States of America High 24297929
2014 GIT1 tyrosine phosphorylation by Src is required for GIT1-eNOS complex formation and eNOS activation. Mutations Y293F and Y554F reduce GIT1 phosphorylation and impair GIT1-eNOS binding and eNOS activation. Akt phosphorylation activates eNOS (Ser1177) and also regulates Src-mediated GIT1 tyrosine phosphorylation and GIT1-eNOS association, downstream of ETB receptor G-protein betagamma subunits. Site-directed mutagenesis of GIT1 (Y293F, Y554F), siRNA, co-immunoprecipitation, Src and Akt inhibitors, NO measurement The Journal of biological chemistry High 24764294
2014 GIT1 and βPIX are required for synaptic GABAAR surface stability through a GIT1/βPIX/Rac1/PAK signaling pathway that modulates F-actin. Disruption of this pathway (by RNAi, dominant-negative, or pharmacological approaches) reduces GABAAR clustering and decreases inhibitory synaptic strength. RNAi, dominant-negative constructs, pharmacological inhibition, GABAAR surface imaging, electrophysiology Cell reports High 25284783
2014 Two tyrosines at positions 246 and 293 in human GIT1 are required to maintain GIT1 in an inactive (binding-incompetent) conformation via intramolecular interaction. Mutation of these residues to alanine or glutamic acid (but not phenylalanine) enhances paxillin binding without affecting betaPIX binding. These tyrosines mediate binding between the amino- and carboxy-terminal fragments of GIT1. Enhanced paxillin binding positively affects cell motility. Site-directed mutagenesis, co-immunoprecipitation, domain fragment reconstitution, transwell migration and wound healing assays PloS one Medium 24699139
2015 MAT2B-GIT1 scaffold activates MEK1/2 not via PAK1 or Src, but by interacting with B-Raf and c-Raf and promoting Raf recruitment to MEK1/2. MAT2B-GIT1 activates Ras (with MAT2B directly interacting with Ras and increasing its stability) and promotes B-Raf/c-Raf heterodimerization; c-Raf is the key mediator of MEK1/2 activation. Co-immunoprecipitation, confocal microscopy, pull-down assays with recombinant proteins, orthotopic liver cancer model, constitutively active B-Raf cell line The American journal of pathology High 25794709
2016 GIT1 forms a novel mTOR complex in astrocytes and neural stem cells that lacks both Raptor and Rictor. GIT1-mTOR binding is regulated by AKT activation and is essential for mTOR-mediated astrocyte survival. Proteomic analysis (mass spectrometry of mTOR complex), co-immunoprecipitation, GIT1 knockdown, AKT inhibitors, cell survival assays Genes & development Medium 27340174
2016 GIT1/betaPIX/PAK1 regulate microtubule nucleation: GIT1 and PAK1 are positive regulators while betaPIX is a negative regulator of microtubule nucleation from interphase centrosomes. GIT1 associates with centrosomes. GIT1, betaPIX, and PAK1 are in complexes with gamma-tubulin. GIT1 directly interacts with gamma-tubulin via its N-terminal domain (centrosome-targeting domain). GIT1 and betaPIX serve as PAK1 substrates in vitro. Microtubule regrowth assay, siRNA depletion, phenotypic rescue, in vitro kinase assay, pull-down assays, immunofluorescence microscopy Biochimica et biophysica acta High 27012601
2016 Rare coding variants of GIT1 found in schizophrenia patients (including GIT1-R283W and GIT1-S601N) are loss-of-function for activating PAK3 and MAPK. GIT1-R283W shows deficits in PAK phosphorylation in hippocampal neurons and reduced GAD1 protein expression induction. An allelic series of rare GIT1 variants shows correlated loss of PAK3 and MAPK activation. Cell-based functional assays, PAK3 and MAPK activation assays, hippocampal neuron culture, site-specific variant expression Molecular psychiatry Medium 27457813
2017 MeCP2 binds to methylated CpG islands in the GIT1 promoter and transcriptionally upregulates GIT1 expression, thereby activating the MEK1/2-ERK1/2 signaling pathway and promoting gastric cancer cell proliferation. Chromatin immunoprecipitation (ChIP)-qRT-PCR, reporter gene assay, microarray analysis, siRNA knockdown Oncogenesis Medium 28759023
2018 GIT1 contributes to osteoclast autophagy by interacting with Beclin1 and promoting Beclin1 phosphorylation at Thr119, which induces disruption of the Beclin1-Bcl2 interaction under starvation conditions, thereby activating autophagy. GIT1 KO mice show reduced osteoclast number and autophagosome formation. GIT1 KO mice, in vitro co-immunoprecipitation, Beclin1 phosphorylation assays, autophagosome/autolysosome quantification, fracture repair model Cell death & disease Medium 30546041
2019 GIT1 enhances NEMO's affinity for K63-linked ubiquitin chains via interaction with NEMO coiled-coil 2 domains, thereby activating NF-κB signaling, which in turn activates Notch (NICD-dependent) signaling in BMSCs to promote VEGF secretion and angiogenesis. Co-immunoprecipitation, shRNA knockdown, NF-κB/Notch reporter assays, nuclear fractionation, GIT1 KO mice Cell proliferation Medium 31502302
2021 GIT1 forms a neuronal signaling complex with mTOR kinase and Raptor that couples synaptic stimuli to mTOR-dependent protein synthesis. GluN3A-containing NMDARs negatively regulate GIT1 binding to mTOR. Silencing GIT1 inhibits synaptic mTOR activation and restricts mTOR-dependent translation of activity-regulated mRNAs. GluN3A removal enables GIT1/mTOR complex formation and potentiates mTOR-dependent protein synthesis and memory consolidation. Co-immunoprecipitation, GluN3A conditional knockout mice, GIT1 siRNA, mTOR activity assays, polysome profiling, behavioral memory tasks eLife High 34787081
2022 Brain-specific GIT1 deletion in mice causes deficits in fear conditioning memory and spatial memory, and reduces cortical neuron dendritic spine density. GIT1 deletion perturbs phosphorylation of specific networks of GIT1-interacting synaptic proteins including several schizophrenia and neurodevelopmental disorder risk genes. Conditional neural-selective GIT1 KO mice, fear conditioning and spatial memory tests, dendritic spine analysis, global quantitative phospho-proteomics Molecular psychiatry High 35505090
2022 GIT1 interacts with the Notch intracellular domain (ICD) and inhibits cytoplasm-to-nucleus transport of the Notch ICD, thereby suppressing Notch signaling. GIT1 knockdown in ER(-) breast tumor cells increases downstream Notch signaling and ALDH activity. GIT1 overexpression prevents Notch-driven tumor formation in xenografts. Co-immunoprecipitation, GIT1 knockdown/overexpression, Notch signaling reporter, nuclear fractionation, xenograft model Nature communications High 35318302

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 A protein interaction network links GIT1, an enhancer of huntingtin aggregation, to Huntington's disease. Molecular cell 339 15383276
2000 Coupling of PAK-interacting exchange factor PIX to GIT1 promotes focal complex disassembly. Molecular and cellular biology 313 10938112
2005 A GIT1/PIX/Rac/PAK signaling module regulates spine morphogenesis and synapse formation through MLC. The Journal of neuroscience : the official journal of the Society for Neuroscience 284 15800193
2018 MSC-derived exosomes promote proliferation and inhibit apoptosis of chondrocytes via lncRNA-KLF3-AS1/miR-206/GIT1 axis in osteoarthritis. Cell cycle (Georgetown, Tex.) 275 30324848
1998 beta2-Adrenergic receptor regulation by GIT1, a G protein-coupled receptor kinase-associated ADP ribosylation factor GTPase-activating protein. Proceedings of the National Academy of Sciences of the United States of America 253 9826657
2006 Paxillin phosphorylation at Ser273 localizes a GIT1-PIX-PAK complex and regulates adhesion and protrusion dynamics. The Journal of cell biology 250 16717130
2002 GIT1 functions in a motile, multi-molecular signaling complex that regulates protrusive activity and cell migration. Journal of cell science 170 11896197
2003 Synapse formation is regulated by the signaling adaptor GIT1. The Journal of cell biology 166 12695502
2013 miRNA-491-5p and GIT1 serve as modulators and biomarkers for oral squamous cell carcinoma invasion and metastasis. Cancer research 146 24335959
2000 Multiple endocytic pathways of G protein-coupled receptors delineated by GIT1 sensitivity. Proceedings of the National Academy of Sciences of the United States of America 144 10655494
2003 Interaction between liprin-alpha and GIT1 is required for AMPA receptor targeting. The Journal of neuroscience : the official journal of the Society for Neuroscience 131 12629171
2007 Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation. Nature neuroscience 123 17310244
2002 S1P induces FA remodeling in human pulmonary endothelial cells: role of Rac, GIT1, FAK, and paxillin. Journal of applied physiology (Bethesda, Md. : 1985) 119 12482769
2011 GIT1 is associated with ADHD in humans and ADHD-like behaviors in mice. Nature medicine 117 21499268
2014 MicroRNA-149 targets GIT1 to suppress integrin signaling and breast cancer metastasis. Oncogene 116 24608434
2001 Identification of GIT1/Cat-1 as a substrate molecule of protein tyrosine phosphatase zeta /beta by the yeast substrate-trapping system. Proceedings of the National Academy of Sciences of the United States of America 100 11381105
2004 GIT1 functions as a scaffold for MEK1-extracellular signal-regulated kinase 1 and 2 activation by angiotensin II and epidermal growth factor. Molecular and cellular biology 80 14701758
2015 MiR-138 inhibits cell proliferation and reverses epithelial-mesenchymal transition in non-small cell lung cancer cells by targeting GIT1 and SEMA4C. Journal of cellular and molecular medicine 72 26283050
2013 MAT2B-GIT1 interplay activates MEK1/ERK 1 and 2 to induce growth in human liver and colon cancer. Hepatology (Baltimore, Md.) 72 23325601
2003 GIT1 mediates Src-dependent activation of phospholipase Cgamma by angiotensin II and epidermal growth factor. The Journal of biological chemistry 71 14523024
2004 GIT1 activates p21-activated kinase through a mechanism independent of p21 binding. Molecular and cellular biology 70 15082779
2005 GIT1 is a scaffold for ERK1/2 activation in focal adhesions. The Journal of biological chemistry 67 15923189
2009 Identification of MYO18A as a novel interacting partner of the PAK2/betaPIX/GIT1 complex and its potential function in modulating epithelial cell migration. Molecular biology of the cell 66 19923322
2005 Thyrotropin receptor trafficking relies on the hScrib-betaPIX-GIT1-ARF6 pathway. The EMBO journal 64 15775968
2009 EphA2 engages Git1 to suppress Arf6 activity modulating epithelial cell-cell contacts. Molecular biology of the cell 61 19193766
2004 GIT1 mediates thrombin signaling in endothelial cells: role in turnover of RhoA-type focal adhesions. Circulation research 59 15016733
2007 Induction of vascular permeability: beta PIX and GIT1 scaffold the activation of extracellular signal-regulated kinase by PAK. Molecular biology of the cell 57 17429073
1998 GIT1, a gene encoding a novel transporter for glycerophosphoinositol in Saccharomyces cerevisiae. Genetics 57 9691030
2014 GIT1 and βPIX are essential for GABA(A) receptor synaptic stability and inhibitory neurotransmission. Cell reports 56 25284783
2017 MeCP2, a target of miR-638, facilitates gastric cancer cell proliferation through activation of the MEK1/2-ERK1/2 signaling pathway by upregulating GIT1. Oncogenesis 54 28759023
2007 Role of phospholipase Cgamma1 in cell spreading requires association with a beta-Pix/GIT1-containing complex, leading to activation of Cdc42 and Rac1. Molecular and cellular biology 52 17562871
2008 Structures of dimeric GIT1 and trimeric beta-PIX and implications for GIT-PIX complex assembly. Journal of molecular biology 50 19136011
2007 GIT1 utilizes a focal adhesion targeting-homology domain to bind paxillin. Cellular signalling 50 17467235
2018 miR-149-5p inhibits cell proliferation and invasion through targeting GIT1 in medullary thyroid carcinoma. Oncology letters 49 30655777
2020 Exosomes derived from GIT1-overexpressing bone marrow mesenchymal stem cells promote traumatic spinal cord injury recovery in a rat model. The International journal of neuroscience 42 32223487
2008 GIT1 mediates VEGF-induced podosome formation in endothelial cells: critical role for PLCgamma. Arteriosclerosis, thrombosis, and vascular biology 42 19023093
2007 Differential expression of the ARF GAP genes GIT1 and GIT2 in mouse tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 40 17565117
2006 betaPIX controls cell motility and neurite extension by regulating the distribution of GIT1. Journal of cell science 39 16787945
2018 GIT1 contributes to autophagy in osteoclast through disruption of the binding of Beclin1 and Bcl2 under starvation condition. Cell death & disease 38 30546041
2014 Endothelial nitric-oxide synthase (eNOS) is activated through G-protein-coupled receptor kinase-interacting protein 1 (GIT1) tyrosine phosphorylation and Src protein. The Journal of biological chemistry 38 24764294
2015 Methionine adenosyltransferase 2B-GIT1 complex serves as a scaffold to regulate Ras/Raf/MEK1/2 activity in human liver and colon cancer cells. The American journal of pathology 37 25794709
2008 GIT1 mediates HDAC5 activation by angiotensin II in vascular smooth muscle cells. Arteriosclerosis, thrombosis, and vascular biology 37 18292392
2015 Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression. International journal of molecular medicine 36 25715677
2013 GluN3A expression restricts spine maturation via inhibition of GIT1/Rac1 signaling. Proceedings of the National Academy of Sciences of the United States of America 36 24297929
2002 Hic-5 interacts with GIT1 with a different binding mode from paxillin. Journal of biochemistry 36 12153727
2010 Impaired spine formation and learning in GPCR kinase 2 interacting protein-1 (GIT1) knockout mice. Brain research 35 20043896
2021 Inhibition of micro RNA miR-122-5p prevents lipopolysaccharide-induced myocardial injury by inhibiting oxidative stress, inflammation and apoptosis via targeting GIT1. Bioengineered 34 34002676
2016 Proteomic analysis reveals GIT1 as a novel mTOR complex component critical for mediating astrocyte survival. Genes & development 34 27340174
2010 GPCR kinase 2 interacting protein 1 (GIT1) regulates osteoclast function and bone mass. Journal of cellular physiology 34 20568227
2012 G-protein-coupled receptor kinase interactor-1 (GIT1) is a new endothelial nitric-oxide synthase (eNOS) interactor with functional effects on vascular homeostasis. The Journal of biological chemistry 33 22294688
2016 MicroRNA-34c Suppresses Breast Cancer Migration and Invasion by Targeting GIT1. Journal of Cancer 31 27698902
2021 Exosomal miR-122-5p inhibits tumorigenicity of gastric cancer by downregulating GIT1. The International journal of biological markers 30 33752480
2016 Functional analysis of rare variants found in schizophrenia implicates a critical role for GIT1-PAK3 signaling in neuroplasticity. Molecular psychiatry 30 27457813
2008 GIT1 paxillin-binding domain is a four-helix bundle, and it binds to both paxillin LD2 and LD4 motifs. The Journal of biological chemistry 30 18448431
2009 Impaired fear response in mice lacking GIT1. Neuroscience letters 29 19383529
2014 Impaired angiogenesis during fracture healing in GPCR kinase 2 interacting protein-1 (GIT1) knock out mice. PloS one 27 24586541
2008 An epidermal growth factor (EGF) -dependent interaction between GIT1 and sorting nexin 6 promotes degradation of the EGF receptor. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27 18523162
2006 Regulation of neuroendocrine exocytosis by the ARF6 GTPase-activating protein GIT1. The Journal of biological chemistry 27 16439353
2019 GIT1 is critical for formation of the CD31hiEmcnhi vessel subtype in coupling osteogenesis with angiogenesis via modulating preosteoclasts secretion of PDGF-BB. Bone 26 30853660
2015 A Critical Role of GIT1 in Vertebrate and Invertebrate Brain Development. Experimental neurobiology 26 25792865
2014 PDGF regulates chondrocyte proliferation through activation of the GIT1- and PLCγ1-mediated ERK1/2 signaling pathway. Molecular medicine reports 26 25175053
2012 Phosphorylation of GIT1 tyrosine 321 is required for association with FAK at focal adhesions and for PDGF-activated migration of osteoblasts. Molecular and cellular biochemistry 26 22302306
2007 Identification of an intramolecular interaction important for the regulation of GIT1 functions. Molecular biology of the cell 26 17898078
2016 GIT1/βPIX signaling proteins and PAK1 kinase regulate microtubule nucleation. Biochimica et biophysica acta 25 27012601
2020 Macrophage GIT1 Contributes to Bone Regeneration by Regulating Inflammatory Responses in an ERK/NRF2-Dependent Way. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 24 32460388
2016 miR-125a-3p targetedly regulates GIT1 expression to inhibit osteoblastic proliferation and differentiation. Experimental and therapeutic medicine 24 28101188
2009 Rac3 inhibits adhesion and differentiation of neuronal cells by modifying GIT1 downstream signaling. Journal of cell science 24 19494130
2006 Identification of protein networks associated with the PAK1-betaPIX-GIT1-paxillin signaling complex by mass spectrometry. Journal of proteome research 24 16944954
2019 GIT1 regulates angiogenic factor secretion in bone marrow mesenchymal stem cells via NF-κB/Notch signalling to promote angiogenesis. Cell proliferation 23 31502302
2012 GIT1 phosphorylation on serine 46 by PKD3 regulates paxillin trafficking and cellular protrusive activity. The Journal of biological chemistry 23 22893698
2016 Effects of platelet-derived growth factor on chondrocyte proliferation, migration and apoptosis via regulation of GIT1 expression. Molecular medicine reports 22 27220359
2008 The Drosophila homologue of Arf-GAP GIT1, dGIT, is required for proper muscle morphogenesis and guidance during embryogenesis. Developmental biology 21 18996366
2006 Phosphorylation of serine 709 in GIT1 regulates protrusive activity in cells. Biochemical and biophysical research communications 21 16797488
2003 Inositol and phosphate regulate GIT1 transcription and glycerophosphoinositol incorporation in Saccharomyces cerevisiae. Eukaryotic cell 21 12912892
2021 UBTF facilitates melanoma progression via modulating MEK1/2-ERK1/2 signalling pathways by promoting GIT1 transcription. Cancer cell international 20 34663332
2011 G protein coupled receptor kinase 2 interacting protein 1 (GIT1) is a novel regulator of mitochondrial biogenesis in heart. Journal of molecular and cellular cardiology 20 21756914
2017 Targeting of GIT1 by miR-149* in breast cancer suppresses cell proliferation and metastasis in vitro and tumor growth in vivo. OncoTargets and therapy 19 29270025
2015 Microtubule nucleation in mouse bone marrow-derived mast cells is regulated by the concerted action of GIT1/βPIX proteins and calcium. Journal of immunology (Baltimore, Md. : 1950) 19 25821222
2009 GIT1 is a novel MEK1-ERK1/2 scaffold that localizes to focal adhesions. Cell biology international 18 19947948
2016 miR-195 inhibits the proliferation and migration of chondrocytes by targeting GIT1. Molecular medicine reports 17 27922692
2015 Converging evidence does not support GIT1 as an ADHD risk gene. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 17 26061966
2014 Phosphorylation of tyrosine 285 of PAK1 facilitates βPIX/GIT1 binding and adhesion turnover. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17 25466889
2018 Alternative RNA splicing of the GIT1 gene is associated with neuroendocrine prostate cancer. Cancer science 16 30417466
2023 Neuroprotective Effect of Mangiferin against Parkinson's Disease through G-Protein-Coupled Receptor-Interacting Protein 1 (GIT1)-Mediated Antioxidant Defense. ACS chemical neuroscience 15 37036451
2006 Schizosaccharomyces pombe Git1 is a C2-domain protein required for glucose activation of adenylate cyclase. Genetics 15 16489217
2014 Decreased BMP2 signal in GIT1 knockout mice slows bone healing. Molecular and cellular biochemistry 14 25138700
2012 Association study of GIT1 gene with attention-deficit hyperactivity disorder in Brazilian children and adolescents. Genes, brain, and behavior 14 22897819
2005 Characterization of the endogenous GIT1-betaPIX complex, and identification of its association to membranes. European journal of cell biology 14 16373173
2021 Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife 13 34787081
2018 RETRACTED: miR-149 regulates the proliferation and apoptosis of cervical cancer cells by targeting GIT1. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 13 30021347
2021 GIT1 protects traumatically injured spinal cord by prompting microvascular endothelial cells to clear myelin debris. Aging 12 33621952
2017 GIT1 gene deletion delays chondrocyte differentiation and healing of tibial plateau fracture through suppressing proliferation and apoptosis of chondrocyte. BMC musculoskeletal disorders 12 28754105
2017 β-PIX plays an important role in regulation of intestinal epithelial restitution by interacting with GIT1 and Rac1 after wounding. American journal of physiology. Gastrointestinal and liver physiology 12 29191942
2014 Identification of two tyrosine residues required for the intramolecular mechanism implicated in GIT1 activation. PloS one 12 24699139
2022 GIT1 protects against breast cancer growth through negative regulation of Notch. Nature communications 11 35318302
2022 Brain-specific deletion of GIT1 impairs cognition and alters phosphorylation of synaptic protein networks implicated in schizophrenia susceptibility. Molecular psychiatry 11 35505090
2018 Inhibiting GIT1 reduces the growth, invasion, and angiogenesis of osteosarcoma. Cancer management and research 10 30555255
2011 Biochemical and functional characterization of the interaction between liprin-α1 and GIT1: implications for the regulation of cell motility. PloS one 10 21695141
2008 Regulation of adaptor protein GIT1 in platelets, leading to the interaction between GIT1 and integrin alpha(IIb)beta3. Biochemical and biophysical research communications 10 18211801
2018 GIT1 regulates synaptic structural plasticity underlying learning. PloS one 9 29554125

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