Affinage

Showing PREX1 — P-REX1 is a alias.

PREX1

Phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 1 protein · UniProt Q8TCU6

Length
1659 aa
Mass
186.2 kDa
Annotated
2026-06-10
91 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P-Rex1 is a large multidomain guanine-nucleotide exchange factor that activates the Rho-family GTPases Rac1, Rac2, Rac3 and RhoG to drive actin remodeling, cell migration, ROS production and invasion across neutrophils, neurons, and cancer cells (PMID:11955434, PMID:16243036, PMID:16243035, PMID:18697831, PMID:24659802). Its defining property is coincidence detection at the plasma membrane: Rac-GEF activity is synergistically and directly stimulated by PtdIns(3,4,5)P3 (via the PH domain) and Gβγ subunits, neither input alone being sufficient for full membrane translocation and activation (PMID:11955434, PMID:17698854). Structural work resolves the underlying logic — in the resting state the PH domain occludes the DH active site, stabilized by DH-DEP1 and PH-4HB interdomain contacts and by IP4 binding, while PIP3 and Gβγ disrupt these autoinhibitory interfaces to expose the Rac-binding surface (PMID:26112412, PMID:31663027, PMID:39082940). Gβγ engages two independent interfaces (DH/PH for activation and the PDZ-PDZ tandem for membrane recruitment), and Gαq/Gα13 suppress signaling by sequestering Gβγ (PMID:30446620, PMID:33412417). Activity is further tuned by a phosphorylation cycle: PP1α docks via an RVxF motif and dephosphorylates inhibitory sites (Ser1165, Ser1001, Ser834) to activate the enzyme (PMID:22242915), RTK-linked inputs drive activating phosphorylation at Ser605/Ser1169 (PMID:21042280, PMID:23899556), while PKCδ (Ser313/Ser319), PKA (Ser436, which impairs membrane binding), and PAKs phosphorylate inhibitory sites, the last forming a delayed negative-feedback loop (PMID:26797121, PMID:27788493, PMID:32661198, PMID:27481946); type I PKA RIα subunits bind the PDZ domains and conversely activate P-Rex1 in a cAMP-dependent manner (PMID:26797121, PMID:30530493). Through ErbB/CXCR4-, IGF-1R- and PI3K-coupled inputs P-Rex1 activates Rac1 to drive a C-RAF/MEK/ERK growth axis and tumorigenesis, and its overexpression is reinforced by ERK-driven transcription and protein stabilization in melanoma (PMID:21172654, PMID:24327733, PMID:27358402, PMID:27418645). P-Rex1 deficiency impairs neutrophil recruitment, melanoblast migration and melanoma metastasis, and contributes to hippocampal LTD and social behavior via a postsynaptic PP1α-P-Rex1-Rac1 pathway controlling AMPA-receptor endocytosis (PMID:16243035, PMID:22109529, PMID:26621702). Beyond catalysis, P-Rex1 acts as a Rac-GEF-independent adaptor that limits agonist-induced GPCR internalization by binding GRK2, controls hepatocyte Gpr21 surface trafficking and mitochondrial glucose metabolism, and supports Fc-receptor-dependent phagocytosis (PMID:41100251, PMID:41046518, PMID:41098722).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2002 High

    Established the existence and core biochemistry of P-Rex1, answering whether a PIP3- and Gβγ-responsive Rac-GEF links PI3K and GPCR inputs in neutrophils.

    Evidence Biochemical purification from neutrophil cytosol with in vitro reconstituted GEF assays and antisense knockdown with ROS readout

    PMID:11955434

    Open questions at the time
    • Substrate specificity among Rac isoforms not resolved
    • Structural basis of synergistic activation unknown
  2. 2005 High

    Genetic loss-of-function defined P-Rex1 as a physiologically required, Rac2-preferring GEF in neutrophil GPCR signaling, linking it to ROS, F-actin and inflammatory recruitment.

    Evidence P-Rex1 knockout mice with PBD pulldown GTPase assays, superoxide assays, and in vivo peritonitis model; replicated independently

    PMID:16243035 PMID:16243036

    Open questions at the time
    • Mechanism of Rac2-over-Rac1 selectivity unclear
    • Only mildly reduced chemotaxis left activation regulation open
  3. 2005 High

    Identified the upstream activators and inhibitors that gate P-Rex1, showing Gβγ isoform selectivity and PKA-driven phosphorylation as an off-switch.

    Evidence In vitro GEF assays with purified Gβγ dimers in lipid vesicles, in vitro PKA kinase assays, and cell-based Rac activation assays

    PMID:16301320 PMID:16301321

    Open questions at the time
    • PKA phosphorylation sites not mapped
    • Mechanism connecting phosphorylation to Gβγ responsiveness unknown
  4. 2005 High

    Extended P-Rex1 function beyond immunity by showing it drives neurotrophin-induced Rac1 activation and neuronal migration during brain development.

    Evidence In situ hybridization, immunofluorescence, siRNA, dominant-negative constructs and in utero electroporation

    PMID:15858067

    Open questions at the time
    • Receptor inputs upstream in neurons not defined
    • Rac isoform usage in neurons unresolved
  5. 2007 High

    Dissected how P-Rex1 reaches the membrane, establishing that Gβγ and PIP3 act synergistically for translocation while inhibitory domains retain it in cytosol.

    Evidence Subcellular fractionation in Sf9 cells with domain mutants and in vitro GEF assays; Co-IP placing P-Rex1 with mTORC2

    PMID:17565979 PMID:17698854

    Open questions at the time
    • Structural basis of intramolecular autoinhibition not yet defined
    • mTORC2 association rests on Co-IP in a single lab
  6. 2008 Medium

    Mapped intramolecular autoinhibitory contacts and tied PKA phosphorylation to disruption of domain-domain interaction and Gβγ binding.

    Evidence Co-IP of domain mutants, in vitro GEF assays, and neuronal localization with GEF-dead rescue experiments

    PMID:18514484 PMID:18697831

    Open questions at the time
    • Atomic structure of autoinhibited state still lacking
    • Single-lab domain-interaction assays
  7. 2010 High

    Placed P-Rex1 at the convergence of RTK and GPCR inputs in cancer, defining a phospho-regulatory cycle and a requirement for tumorigenesis.

    Evidence siRNA knockdown, Rac1 activation assays, phospho-specific antibodies, xenografts, and CXCR4/PI3Kγ epistasis in breast cancer cells

    PMID:21042280 PMID:21172654

    Open questions at the time
    • Identity of kinases for individual activating sites not fully resolved
    • Direct versus indirect ErbB-P-Rex1 coupling unclear
  8. 2011 High

    Demonstrated developmental and metastatic roles in melanocyte lineage and broadened substrate/cellular contexts to adipocyte GLUT4 trafficking and platelets.

    Evidence P-Rex1 knockout melanoma model, GLUT4/glucose uptake assays in adipocytes, and Rac1-pulldown mass spectrometry in platelets

    PMID:21884615 PMID:22002247 PMID:22109529

    Open questions at the time
    • Why P-Rex1 is dispensable in platelets despite Rac1 binding unexplained
    • Tissue-specific upstream activators not defined
  9. 2012 High

    Identified PP1α as a direct activating phosphatase and mapped its dephosphorylation sites, establishing reversible phospho-control of GEF activity.

    Evidence In vitro GEF assays with purified PP1α, RVxF motif analysis, MS phosphosite mapping, and S1165A mutagenesis; zebrafish Nodal/Prex1 morpholino study

    PMID:22242915 PMID:22945937

    Open questions at the time
    • Coordination between PP1α and antagonizing kinases in vivo unclear
    • Spatial control of dephosphorylation unknown
  10. 2013 High

    Defined the Rac1/C-RAF/MEK/ERK signaling axis downstream of P-Rex1 in PI3K-pathway-mutant cancers and identified PDGFRβ as a complex partner driving invasion.

    Evidence siRNA, constitutively active Rac1 rescue, PI3K-inhibitor treatment, phospho-ERK/BIM assays, xenografts, and Co-IP in fibroblasts

    PMID:23382862 PMID:23899556 PMID:24327733

    Open questions at the time
    • Whether ERK activation is fully RAS-independent in all contexts unresolved
    • PDGFRβ complex stoichiometry undefined
  11. 2014 High

    Showed P-Rex1 is also a RhoG-GEF defining a P-Rex1→RhoG→DOCK2→Rac hierarchy, and acts in a positive feedback loop upstream of PI3K in cancer.

    Evidence In vitro RhoG GEF assays, P-Rex1 and RhoG knockout neutrophils with DOCK2 recruitment readouts, and phosphoproteomics with gain/loss of function

    PMID:24659802 PMID:25284585

    Open questions at the time
    • Direct mechanism of PI3K-upstream feedback unclear
    • Relative contribution of Rac- versus RhoG-GEF activity per tissue unresolved
  12. 2015 High

    Provided the first atomic view of the DH-PH·Rac1 catalytic complex and connected a PP1α-P-Rex1-Rac1 pathway to synaptic plasticity and autism-like behavior.

    Evidence X-ray crystallography at 1.95 Å with interface mutagenesis; conditional KO with LTD electrophysiology, AMPAR endocytosis, and behavioral assays

    PMID:26112412 PMID:26621702

    Open questions at the time
    • Full-length autoinhibited architecture not yet solved
    • How PIP3/Gβγ release inhibitory domains shown only by inference
  13. 2016 High

    Expanded the regulatory network with direct activators (Norbin, RIα) and inhibitory kinases (PKCδ, PAKs), and confirmed GEF activity drives ERK-dependent proliferation and a melanoma feedforward loop.

    Evidence Purified-protein binding and GEF assays, phospho-site mutagenesis (S436A, S313A), PAK inhibitors with MS, GEF-dead controls, xenografts, and ERK-inhibitor manipulation

    PMID:26792863 PMID:26797121 PMID:27358402 PMID:27418645 PMID:27481946 PMID:27788493

    Open questions at the time
    • Integration of competing positive and negative regulators in time/space not modeled
    • Distinct kinases for each serine only partially assigned
  14. 2018 Medium

    Resolved how Gα subunits restrain P-Rex1 by Gβγ sequestration and detailed GRK2/CXCR4-PI3Kγ recruitment driving T-cell cytokine output.

    Evidence Pulldown with chimeric Gα constructs, DREADD chemogenetics, Co-IP of active complexes, siRNA epistasis, and cytokine/mRNA stability assays

    PMID:30018141 PMID:30446620

    Open questions at the time
    • Stoichiometry of Gβγ sequestration in cells unclear
    • GRK2 binding role versus catalytic recruitment not separated here
  15. 2019 High

    Cryo-EM of the P-Rex1·Gβγ complex revealed a Legionella-phosphatase-like C-terminal fold forming an extensive Gβγ docking site and allosteric activation.

    Evidence Cryo-EM at 3.2 Å, HDX-MS, and functional activation assays

    PMID:31663027

    Open questions at the time
    • Membrane-bound active conformation not captured
    • Coupling of Gβγ docking to active-site exposure incompletely defined
  16. 2020 High

    Solved the DEP1 autoinhibition mechanism, showed PKA acts on membrane binding rather than catalysis directly, and demonstrated PH-domain small-molecule inhibition.

    Evidence Crystal structure of DEP1 at 3.1 Å, liposome binding, in vitro GEF assays with fragments, DSF screen with neutrophil and zebrafish validation; β-cell siRNA insulin secretion study

    PMID:31900312 PMID:32661198 PMID:33347743

    Open questions at the time
    • Full-length autoinhibited structure still pending
    • Selectivity and pharmacology of PH-domain inhibitors not optimized
  17. 2021 Medium

    Separated Gβγ-mediated recruitment from activation, assigning the PDZ-PDZ tandem to membrane targeting and the DH/PH interface to catalytic activation.

    Evidence Domain-fragment pulldowns and a synthetic chimeric RhoGEF (Q-Rhox) with Co-IP

    PMID:33412417

    Open questions at the time
    • Quantitative contribution of each interface in vivo unresolved
    • Dissection relies on chimeric constructs in a single lab
  18. 2024 High

    Defined the complete autoinhibited architecture and its release mechanism, showing the PH domain occludes the DH active site and PIP3 disrupts DH-DEP1/PH-4HB interfaces to activate the enzyme.

    Evidence Cryo-EM of P-Rex1·IP4, HDX-MS, interface-mutant GEF and liposome assays, and cellular gain-of-function migration validation; pSTAT5/IL-7 T-cell study

    PMID:38329813 PMID:39082940

    Open questions at the time
    • Order of PIP3 and Gβγ engagement during activation not fully kinetically resolved
    • How phospho-regulation maps onto the autoinhibited structure unclear
  19. 2025 High

    Genetic separation of catalytic from adaptor functions revealed Rac-GEF-independent roles in limiting GPCR internalization, controlling hepatocyte Gpr21/glucose metabolism, and supporting Fc-receptor phagocytosis.

    Evidence Catalytically inactive Prex1GD knock-in mice with GPCR internalization, in vitro GRK2 binding, hepatocyte metabolic assays, Gpr21 trafficking, and phagocytosis/bactericidal assays

    PMID:41046518 PMID:41098722 PMID:41100251

    Open questions at the time
    • Molecular mechanism by which P-Rex1 blocks GPCR phosphorylation undefined
    • How a single scaffold mediates distinct GEF-independent outputs unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the full regulatory layers — autoinhibition, phospho-cycling, multi-interface Gβγ engagement, and Rac-GEF-independent adaptor functions — are integrated spatiotemporally within a single cell remains unresolved.
  • No unified kinetic model linking activation inputs to output selectivity
  • Structural basis of adaptor (GEF-independent) functions uncharacterized
  • Direct Mendelian disease causation not established in the corpus

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0008092 cytoskeletal protein binding 4 GO:0008289 lipid binding 4 GO:0098772 molecular function regulator activity 3 GO:0060090 molecular adaptor activity 2
Localization
GO:0005829 cytosol 4 GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 3
Partners
GRK2GΒΓNORBIN (NCDN)NRBP1PDGFRΒPP1ΑRAC1RIΑ (PRKAR1A)
Complex memberships
P-Rex1-Gβγ complexmTORC2

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2002 P-Rex1 is a 185 kDa guanine-nucleotide exchange factor (GEF) for Rac, purified from neutrophil cytosol, whose Rac-GEF activity is directly, substantially, and synergistically activated by PtdIns(3,4,5)P3 and Gβγ subunits both in vitro and in vivo. Antisense knockdown of P-Rex1 reduced C5a-stimulated reactive oxygen species formation in a neutrophil-like cell line. Biochemical purification from neutrophil cytosol, in vitro GEF activity assay, antisense knockdown with ROS readout Cell High 11955434
2005 P-Rex1 preferentially activates Rac2 over Rac1 in mouse neutrophils; P-Rex1-deficient neutrophils show impaired Rac2 (but not Rac1) activation in response to fMLP, reduced F-actin formation, superoxide production, and chemotactic migration rate. P-Rex1 showed higher affinity for dominant-negative Rac2(S17N) than Rac1(S17N) by co-immunoprecipitation. P-Rex1 knockout mouse, PBD pulldown GTPase activation assay, co-immunoprecipitation with dominant-negative Rac isoforms, superoxide assay Current biology : CB High 16243035 16243036
2005 In P-Rex1-deficient mice, GPCR-dependent Rac2 activation is impaired; LPS-primed P-Rex1−/− neutrophils lack GPCR-dependent ROS formation; recruitment of P-Rex1−/− neutrophils to inflammatory sites is impaired. Chemotaxis of isolated neutrophils is only mildly reduced, with normal polarization and directionality. P-Rex1 knockout mouse, in vivo peritonitis model, ROS assay, chemotaxis assay Current biology : CB High 16243035
2005 PKA phosphorylates P-Rex1 in vitro and in cells, making Gβγ 47-fold less potent at activating phosphorylated P-Rex1 compared to dephosphorylated P-Rex1. Gs-coupled receptor activation (isoproterenol) increases P-Rex1 phosphorylation and reduces GTP-bound Rac in cells. In vitro kinase assay with purified PKA, 32P metabolic labeling in HEK293T cells, GTP-Rac pulldown assay The Journal of biological chemistry High 16301320
2005 Among Gβγ dimer isoforms, Gβ1–4/γ2 dimers activate P-Rex1 GEF activity (EC50 10–20 nM) while Gβ5γ2 cannot. Gβ1 paired with different γ subunits shows variable potency; Gβ1γ11 (abundant in hematopoietic cells) and Gβ1γ12 are less effective activators. Gα subunits (Gs, Gi, Gq, G12, G13) do not activate P-Rex1. In vitro GEF activity assay with purified recombinant Gβγ dimers reconstituted into synthetic lipid vesicles The Journal of biological chemistry High 16301321
2005 P-Rex1 is expressed in developing mouse brain neurons and localizes to the leading process of migrating neurons. In PC12 cells, P-Rex1 is activated by NGF to increase GTP-bound Rac1 and cell motility. Dominant-negative P-Rex1 (lacking DH domain) or siRNA knockdown impairs neurotrophin/EGF-induced cell migration of PC12 cells and primary cortical neurons. In utero electroporation of the dominant-negative form perturbs radial neuronal migration. In situ hybridization, immunofluorescence localization, Rac-GTP pulldown, siRNA knockdown, dominant-negative construct, in utero electroporation The Journal of neuroscience High 15858067
2007 P-Rex1 membrane translocation requires synergistic action of Gβγ and PI3K (PIP3); neither alone causes significant translocation. The DH/PH domain tandem is sufficient for membrane localization; GEF activity is not required. The DEP, PDZ, and IP4P domains promote cytosolic retention in basal cells. Membrane-derived P-Rex1 has higher basal Rac2-GEF activity than cytosol-derived P-Rex1. Subcellular fractionation of Sf9 cells co-expressing P-Rex1 with Gβγ and/or PI3K; P-Rex1 domain mutants; in vitro Rac2-GEF activity assay The Journal of biological chemistry High 17698854
2007 P-Rex1 interacts with mTOR through its tandem DEP domains and is associated with both mTORC1 and mTORC2 complexes. P-Rex1 dominant-negative constructs and shRNA knockdown decrease mTOR-dependent leucine-induced Rac activation and cell migration. P-Rex1 is only active when in the mTORC2 complex (rapamycin does not inhibit Rac activity or migration induced by leucine). Co-immunoprecipitation of P-Rex1 with mTOR complexes, dominant-negative constructs, shRNA knockdown, Rac activation assay, cell migration assay The Journal of biological chemistry Medium 17565979
2007 Endogenous P-Rex1 translocates from cytoplasm to the leading edge of polarized human neutrophils upon chemoattractant stimulation, colocalizing with F-actin and Rac2, in a Gβγ- and PIP3-dependent manner. This translocation requires tyrosine kinase activity, is modulated by cell adhesion, and is inhibited by PKA activation. Immunofluorescence microscopy of endogenous P-Rex1 in activated human neutrophils, pharmacological inhibitors Journal of leukocyte biology Medium 17227822
2008 The second DEP and first PDZ domains of P-Rex1 associate with the IP4P domain (intramolecular interaction). Mutations in the PDZ protein-binding pocket or C-terminal truncation of IP4P abolish this interaction. Gβγ can activate a complex of P-Rex1 lacking IP4P together with isolated IP4P domain, as well as full-length P-Rex1. PKA phosphorylation prevents domain-domain interaction and Gβγ binding. Co-immunoprecipitation of P-Rex1 domain mutants, in vitro GEF assay, PAK1/2 phosphorylation assay, actin reorganization assay Cellular signalling Medium 18514484
2008 P-Rex1 localizes to distal tips of developing neurites and growth cones of hippocampal neurons. P-Rex1 expression inhibits NGF-stimulated neurite differentiation in PC12 cells via its Rac-GEF activity; low-dose cytochalasin D rescues this. P-Rex1 activates Rac3 GTPase in PC12 cells. siRNA knockdown of P-Rex1 reduces Rac1 and Rac3 activity and promotes spontaneous neurite formation and NGF-induced hyper-elongation. Immunofluorescence localization, siRNA knockdown, GTPase activation assays (Rac1 and Rac3), GEF-dead mutant, cytochalasin D treatment Journal of cell science Medium 18697831
2009 P-Rex1 PDZ domains interact directly with the carboxyl-terminal tail of S1P receptor S1P1 (including full-length receptor monomers and dimers). Co-expression of P-Rex1 reduces S1P1 trafficking to intracellular compartments, and expression of P-Rex1 PDZ domains increases endothelial cell migration to S1P. Co-immunoprecipitation, cell surface trafficking assay, migration assay with PDZ domain expression Biochemical and biophysical research communications Medium 20036214
2010 P-Rex1 is required for ErbB receptor-driven Rac1 activation, motility, cell growth, and tumorigenesis in breast cancer cells. Activation of P-Rex1 in breast cancer cells requires convergent inputs from ErbB receptors and a Gβγ/PI3Kγ-dependent pathway. The GPCR CXCR4 is identified as a mediator of P-Rex1/Rac1 activation in response to ErbB ligands. siRNA knockdown, Rac1 activation assay (GTP pulldown), cell motility assay, xenograft tumor model, epistasis using PI3Kγ and CXCR4 manipulation Molecular cell High 21172654
2010 ErbB/HER receptor activation triggers a phosphorylation/dephosphorylation cycle of P-Rex1. Dephosphorylation of inhibitory residues (Ser313, Ser319) and phosphorylation of activating residues (Ser605, Ser1169) together promote Rac activation. P-Rex1 knockdown impairs breast cancer cell migration/invasion and in vivo tumorigenic potential. Phospho-specific antibody analysis, siRNA knockdown, Rac activation assay, in vivo tumor assay Oncogene Medium 21042280
2010 P-Rex1 and Vav1 cooperate synergistically in controlling fMLF-stimulated Rac1 and Rac2 activation, ROS formation, adhesion, and chemotaxis in neutrophils. Double-deficient P-Rex1/Vav1 neutrophils show more severe impairment than single knockouts or other combinations, with reduced Mac-1 surface expression. Double-knockout mouse genetics, Rac1/Rac2 activation assays, ROS assay, adhesion/chemotaxis assays Journal of immunology High 21178006
2011 P-Rex1 deficiency causes a melanoblast migration defect during development (white belly phenotype) and P-Rex1−/− mice are resistant to melanoma metastasis in a murine melanoma model. P-Rex1 drives invasion in a Rac-dependent manner. P-Rex1 knockout mouse crossed to melanoma model, developmental phenotype scoring, invasion assay with Rac pathway readout Nature communications High 22109529
2011 P-Rex1 promotes GLUT4 trafficking to the plasma membrane in adipocytes at submaximal insulin concentrations in a PI3K- and Rac1-dependent manner. This requires a functional actin network and membrane ruffle formation; Cdc42 or Rho expression did not affect P-Rex1-mediated GLUT4 trafficking. P-Rex1 siRNA knockdown or dominant-negative mutant reduced glucose uptake. siRNA knockdown, dominant-negative P-Rex1, GLUT4 trafficking assay, actin disruption (cytochalasin D), glucose uptake assay in 3T3-L1 adipocytes The Journal of biological chemistry Medium 22002247
2011 P-Rex1 is expressed in platelets and associates with Rac1 (identified by mass spectrometry from Rac1 pulldown of platelet lysates). However, platelets from P-Rex1−/− mice respond normally to platelet agonists and activating surfaces, indicating P-Rex1 is not required for Rac1-mediated platelet activation. Mass spectrometry of Rac1-associated proteins, western blot, P-Rex1 knockout platelet function assays (spreading, aggregation) Journal of molecular signaling Medium 21884615
2012 PP1α binds P-Rex1 through an RVxF-type docking motif and directly activates P-Rex1 GEF activity in vitro, additively to PIP3 and Gβγ. PP1α also activates P-Rex1 in vivo. Mass spectrometry identified three PP1α dephosphorylation sites on P-Rex1: Ser834, Ser1001, and Ser1165. Mutagenesis of Ser1165 to alanine activated P-Rex1 similarly to PP1α, confirming it as a key inhibitory phosphorylation site. In vitro GEF activity assay with purified PP1α and P-Rex1, RVxF docking motif analysis, mass spectrometry phosphosite identification, site-directed mutagenesis The Biochemical journal High 22242915
2012 In zebrafish gastrulation, the Rac-specific GEF Prex1 is a Nodal signaling target and mediates Nodal-dependent random motility of endodermal cells. Reducing Rac1 activity in endoderm cells caused them to bypass random migration and aberrantly contribute to mesodermal tissues. Zebrafish transgenic line for actin visualization, morpholino knockdown of prex1, Rac1 inhibition, cell fate analysis The Journal of cell biology Medium 22945937
2013 P-Rex1 is the PIP3-dependent GEF for Rac1 responsible for regulation of the Rac1/C-RAF/MEK/ERK pathway (not involving RAS) in PIK3CA-mutant and HER2-amplified breast cancers. PI3K inhibition suppresses this Rac1/PAK/C-RAF/MEK/ERK axis, leading to BIM upregulation and apoptosis. Constitutively active Rac1 expression blocked PI3Ki-induced ERK suppression and apoptosis. siRNA knockdown of P-Rex1, constitutively active Rac1 rescue, PI3K inhibitor treatment, phospho-ERK/MEK/BIM assays, in vivo xenograft Proceedings of the National Academy of Sciences of the United States of America High 24327733
2013 P-Rex1 and PDGFRβ are components of the same macromolecular complex (co-immunoprecipitation). P-Rex1 expression drives invasion in fibroblasts in a PDGFRβ-dependent manner; siRNA of either P-Rex1 or PDGFRβ opposes invasiveness in melanoma cells. Co-immunoprecipitation, siRNA knockdown, 3D invasion assay PloS one Medium 23382862
2013 Phosphorylation of P-Rex1 at Ser1169 is induced by IGF-1R and FGFR activation and is required for IGF-1-induced Rac activation and cell proliferation, as well as IGF-1-induced adhesion in MCF7 breast cancer cells. Phospho-specific antibody analysis, siRNA knockdown, Rac activation assay, proliferation and adhesion assays Cellular signalling Medium 23899556
2014 P-Rex1 acts as a GEF for RhoG both in vitro and in GPCR-stimulated primary mouse neutrophils, in addition to its known Rac-GEF activity. Loss of either P-Rex1 or RhoG caused equivalent reductions in GPCR-driven Rac activation and NADPH oxidase activity. Loss of RhoG impaired GPCR-driven recruitment of the Rac-GEF DOCK2 and F-actin to the leading edge, establishing a signaling hierarchy: P-Rex1→RhoG→DOCK2→Rac. In vitro GEF activity assay for RhoG, primary neutrophils from P-Rex1 and RhoG knockout mice, NADPH oxidase assay, F-actin localization, DOCK2 recruitment assay Journal of cell science High 24659802
2014 P-REX1 overexpression activates Rac1 and increases PI3K/AKT, MEK/ERK signaling and IGF-1R activation in a PTEN-independent manner. Loss of P-REX1 suppresses PI3K/AKT and MEK/ERK. P-REX1 provides positive feedback to activators upstream of PI3K. P-Rex1 overexpression/knockdown, phosphoproteomic analysis, Rac1 activation assay, IGF-1R activation assay Oncogene Medium 25284585
2015 Crystal structure of the P-Rex1 DH-PH tandem domain in complex with Rac1 at 1.95 Å resolution. Interface mutagenesis revealed a critical role for the P-Rex1·Rac1 complex in signaling downstream of RTKs and GPCRs. Structural analysis indicated PIP3/Gβγ binding sites are on the opposite surface from the Rac1 interface, supporting a model whereby PIP3/Gβγ binding releases inhibitory C-terminal domains to expose the Rac1 binding site. X-ray crystallography (1.95 Å), interface mutagenesis with functional signaling readouts The Journal of biological chemistry High 26112412
2015 Genetic deletion or knockdown of P-Rex1 in the CA1 hippocampus causes autism-like social behavior linked to defective LTD via alteration of AMPA receptor endocytosis mediated by a postsynaptic PP1α-P-Rex1-Rac1 signaling pathway. Conditional knockout, hippocampal siRNA knockdown, LTD electrophysiology, AMPA receptor endocytosis assay, behavioral testing Proceedings of the National Academy of Sciences of the United States of America High 26621702
2016 Norbin (Neurochondrin, NCDN) is a direct binding partner of P-Rex1, interacting through the PH domain of P-Rex1. Direct interaction with Norbin increases the basal, PIP3-, and Gβγ-stimulated Rac-GEF activity of P-Rex1. Co-expression of P-Rex1 and Norbin induces translocation of both proteins from cytosol to plasma membrane and promotes cell spreading and lamellipodia formation. Pulldown from brain fractions, co-immunoprecipitation, in vitro binding with purified recombinant proteins, in vitro Rac-GEF assay, PAK-CRIB pulldown, immunofluorescence and subcellular fractionation The Journal of biological chemistry High 26792863
2016 Type I PKA regulatory subunit RIα interacts with P-Rex1 PDZ domains via the CNB-B domain of RIα. P-Rex1 activation localizes PKA to the cell periphery. PKA phosphorylates the P-Rex1 DEP1 domain at Ser436, which inhibits the DH-PH catalytic cassette by direct interaction. A P-Rex1 S436A mutant shows increased RacGEF activity and prevents the inhibitory effect of PKA on cell migration. Co-immunoprecipitation of endogenous proteins, PKA activity assays, phospho-site mutagenesis (S436A), Rac-GEF activity assay, endothelial cell migration assay The Journal of biological chemistry High 26797121
2016 PAK kinases phosphorylate PREX1 downstream of insulin, neuregulin, and IGF-1 receptor stimulation. PAK-mediated phosphorylation reduces PREX1 binding to PIP3 and negatively regulates PREX1 GEF activity. PREX1 phosphorylation onset is delayed compared to AKT, supporting a negative feedback model. GPCR-stimulated PREX1 phosphorylation is partially PAK-dependent and also involves PKA. PAK inhibitors, phospho-mass spectrometry, PIP3 binding assay, in vitro GEF activity assay The Journal of biological chemistry Medium 27481946
2016 PKC isoform PKCδ directly phosphorylates P-Rex1 at Ser313. PKC activation causes phosphorylation of Ser313, Ser319, and Ser1169. Phosphorylation at Ser313 negatively regulates P-Rex1 exchange activity. Growth factor receptor-induced Ser1169 phosphorylation occurs through a mechanism independent of PKC, indicating different kinases control different regulatory serines. In vitro kinase assay with purified PKCδ, phospho-specific antibody analysis, P-Rex1 mutant expression (S313A), GEF activity assay Oncotarget Medium 27788493
2016 PREX1 GEF activity drives ERK1/2 MAPK activation downstream of EGF/IGF-1 stimulation, promoting cyclin D1 and p21(WAF1) induction and anchorage-independent cell growth. GEF-dead PREX1 fails to increase ERK1/2 phosphorylation, anchorage-independent growth, or xenograft tumor growth. MEK1/2/ERK1/2 inhibition suppresses PREX1-mediated effects. Wild-type vs GEF-dead PREX1 expression, shRNA knockdown, phospho-ERK1/2 assay, anchorage-independent growth assay, xenograft tumor model The Journal of biological chemistry High 27358402
2016 ERK/MAPK signaling drives PREX1 overexpression in BRAF- and NRAS-mutant melanoma by both increasing PREX1 gene transcription and promoting PREX1 protein stability. Pharmacologic ERK inhibition reduces PREX1 transcription and protein levels. PREX1-dependent invasion in melanoma is attributable to RAC1 but not CDC42 activation. ERK pathway inhibitors, siRNA knockdown, RAC1/CDC42 activation assays, invasion assay Molecular cancer research : MCR Medium 27418645
2018 Gαq and Gα13 directly inhibit Gβγ signaling to P-REX1. GTPase-deficient GαqQL and Gα13QL form stable complexes with Gβγ, preventing its interaction with P-REX1. Gβγ and AKT kinase associate with active P-REX1 during SDF-1/CXCL12 stimulation. GαqQL and Gα13QL also prevent CXCR4-dependent cell migration. Pulldown assays with chimeric Gα constructs, DREADDs chemogenetic control, co-immunoprecipitation of active P-REX1 complexes, cell migration assay The Journal of biological chemistry Medium 30446620
2018 GRK2 mediates TCR-induced phosphorylation of CXCR4 at Ser339 and TCR-CXCR4 complex formation. This complex signals via PI3Kγ to recruit PREX1 to the membrane, which activates a Rac1-dependent pathway stabilizing cytokine mRNAs and promoting robust cytokine secretion by T cells. siRNA depletion of GRK2, PI3Kγ, and PREX1; phospho-CXCR4 assay; membrane recruitment of PREX1 by fractionation; cytokine ELISA; mRNA stability assay The Journal of biological chemistry Medium 30018141
2018 PKA regulatory subunit RIα directly activates P-REX1 in vitro and promotes P-REX1-mediated Rac activation and cell migration via Gs-coupled EP2 receptors in a cAMP-dependent manner. RIα interacts with P-REX1 PDZ domains via its CNB-B domain. Active P-REX1 fraction is not phosphorylated, while inactive P-REX1 is phosphorylated, indicating co-existence of stimulatory (RIα) and inhibitory (catalytic subunit Cα) PKA effects. In vitro activation assay with purified RIα and P-REX1, cAMP pulldown, siRNA knockdown of RIα, Rac activation assay, endothelial cell migration assay The Journal of biological chemistry High 30530493
2019 Cryo-EM structure of the P-Rex1-Gβγ complex at 3.2 Å reveals that the C-terminal half of P-Rex1 adopts a fold similar to Legionella phosphoinositide phosphatases, forming an extensive docking site for Gβγ together with a DEP domain and two PDZ domains. Hydrogen-deuterium exchange MS suggests Gβγ binding induces allosteric changes in P-Rex1. Functional assays indicate membrane localization is also required for full activation. Cryo-EM structure determination (3.2 Å), hydrogen-deuterium exchange mass spectrometry, functional activation assays Science advances High 31663027
2020 The DEP1 domain of P-Rex1 autoinhibits the DH/PH catalytic module through direct interaction. Crystal structure of DEP1 at 3.1 Å shows a domain-swap involving an exposed basic loop containing the primary PKA phosphorylation site (Ser436). PKA phosphorylation of DEP1 does not affect DH/PH-DEP1 fragment activity in solution but inhibits DEP1 domain binding to phosphatidic acid-containing liposomes, suggesting PKA inhibits P-Rex1 membrane binding rather than its catalytic activity directly. Crystal structure (3.1 Å), in vitro GEF activity assay with DH/PH-DEP1 fragments, liposome binding assay, PKA phosphorylation The Journal of biological chemistry High 32661198
2020 Small molecules targeting the P-Rex1 PH domain block PIP3 binding and inhibit fMLP-induced spreading and Rac2 activation in human neutrophils. One compound reduces neutrophil velocity and inhibits neutrophil recruitment to inflammation in a zebrafish model. Differential scanning fluorimetry screen, PIP3 competition binding assay, human neutrophil spreading/Rac2 activation assay, zebrafish in vivo inflammation assay Molecular pharmacology Medium 31900312
2020 P-Rex1 is expressed in pancreatic β-cells (INS-1 832/13 cells, rat and human islets). siRNA-mediated knockdown of P-Rex1 attenuates glucose-induced Rac1 activation, membrane association, and insulin secretion. RhoG knockdown did not affect glucose-stimulated insulin secretion. siRNA knockdown, Rac1 activation pulldown assay, membrane fractionation, ELISA for insulin secretion Cellular physiology and biochemistry Medium 33347743
2021 Gβγ recruits and activates P-Rex1 via two independent binding interfaces: Gβγ binds both the P-Rex1 DH/PH domains and the PDZ-PDZ tandem. The DEP-DEP tandem and PDZ-PDZ interact intramolecularly and dissociate upon Gβγ binding. The PDZ-PDZ interface mediates P-Rex1 recruitment to the plasma membrane; the DH/PH interface is required for activation. Pulldown assays with domain fragments, synthetic chimeric RhoGEF (Q-Rhox) to dissect recruitment from activation, co-immunoprecipitation Biochemical and biophysical research communications Medium 33412417
2023 NRBP1 (a pseudokinase) binds P-Rex1 and acts as a scaffold to enhance GTP-bound Rac1 and Cdc42 levels in a P-Rex1-dependent manner. NRBP1 overexpression-driven cell migration and invasion are P-Rex1-dependent. ROS generation via a NRBP1/P-Rex1 pathway contributes to oncogenic roles in triple-negative breast cancer. BioID/MS proximity proteomics, co-immunoprecipitation, Rac1/Cdc42 activation assays, siRNA knockdown epistasis, invasion assay, ROS assay Oncogene Medium 36693952
2023 P-Rex1 is a novel substrate of the E3 ubiquitin ligase Malin (EPM2B); Malin ubiquitinates P-Rex1 and this is associated with altered glucose uptake relevant to Lafora disease pathology. Unbiased E3 ligase substrate identification approach, ubiquitination assay, glucose uptake functional assay Neurobiology of disease Medium 36638890
2024 Cryo-EM structure of P-Rex1·IP4 complex reveals an autoinhibited conformation where the PH domain occludes the DH domain active site, stabilized by DH-DEP1 and PH-4HB interdomain contacts. IP4 inhibits P-Rex1 GEF activity and reduces backbone dynamics broadly. Disruption of DH-DEP1 or PH-4HB interfaces increases activity and confers a more extended conformation. Mutations constraining the occluded conformation reduce GEF activity. PIP3-containing liposomes disrupt these interfaces and increase dynamics. This autoinhibited structure is confirmed in living cells by gain-of-function variants showing enhanced activity during chemokine-induced migration. Cryo-EM structure, HDX-MS, in vitro GEF activity assays with interface mutants, liposome binding assay, cell migration assay with interface mutant variants eLife High 39082940
2024 PREX1 promotes nuclear translocation of phosphorylated STAT5 in naive CD4+ T cells, supporting homeostatic proliferation in response to IL-7, and biases differentiation toward effector T cells. PREX1 expression analysis in aged naive CD4+ T cells, nuclear fractionation for phospho-STAT5, functional proliferation assays with PREX1 manipulation JCI insight Medium 38329813
2025 P-Rex1 limits GPCR (S1PR1, CXCR4, PAR4, GLP1R) internalization independently of its Rac-GEF activity, through its PDZ, DEP, and IP4P domains. P-Rex1 blocks phosphorylation required for GPCR internalization. P-Rex1 binds GRK2 both in vitro and in cells, but does not regulate GRK2 activity. Catalytically inactive Prex1GD knock-in mice, GPCR internalization assays, phosphorylation assays, in vitro binding of P-Rex1 with GRK2, domain deletion analysis Cell reports High 41100251
2025 P-Rex1 limits hepatocyte glucose uptake and mitochondrial ATP production independently of its Rac-GEF catalytic activity through the orphan GPCR Gpr21. P-Rex1 controls Gpr21 trafficking (retaining it at plasma membrane) and controls Glut2 surface levels, mitochondrial morphology, membrane potential, and ATP production in hepatocytes. P-Rex1 GEF activity is required for maintaining fasting blood glucose and insulin sensitivity. Prex1−/− and catalytically inactive Prex1GD mice, high-fat diet diabetes model, hepatocyte glucose uptake assay, mitochondrial membrane potential/ATP assays, Gpr21 trafficking by cell fractionation, Glut2 surface assay, pharmacological Gpr21 inverse agonist (GRA2) Cell reports High 41046518
2025 P-Rex1 mediates phagocytosis of IgG-opsonized particles and bactericidal activity in neutrophils independently of its Rac-GEF catalytic activity, through mechanisms not related to its GPCR trafficking or glucose uptake adaptor functions. P-Rex1 mediates both integrin-dependent and Fc receptor-dependent phagocytosis and the Fc receptor-dependent activation of Rac and Syk. P-Rex1 GEF activity is required for migration, ROS, and NET formation. Prex1−/− and catalytically inactive Prex1GD mice, phagocytosis assays (IgG-opsonized zymosan), in vivo septic peritonitis bacteria clearance, Syk activation assay, Rac activation assay Frontiers in immunology High 41098722

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 P-Rex1, a PtdIns(3,4,5)P3- and Gbetagamma-regulated guanine-nucleotide exchange factor for Rac. Cell 448 11955434
2013 PI3K regulates MEK/ERK signaling in breast cancer via the Rac-GEF, P-Rex1. Proceedings of the National Academy of Sciences of the United States of America 185 24327733
2010 Identification of the Rac-GEF P-Rex1 as an essential mediator of ErbB signaling in breast cancer. Molecular cell 173 21172654
2011 P-Rex1 is required for efficient melanoblast migration and melanoma metastasis. Nature communications 154 22109529
2005 P-Rex1 regulates neutrophil function. Current biology : CB 142 16243035
2007 P-Rex1 links mammalian target of rapamycin signaling to Rac activation and cell migration. The Journal of biological chemistry 130 17565979
2009 Upregulation of PIP3-dependent Rac exchanger 1 (P-Rex1) promotes prostate cancer metastasis. Oncogene 129 19305425
2005 P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Current biology : CB 110 16243036
2005 Involvement of a Rac activator,P-Rex1, in neurotrophin-derived signaling and neuronal migration. The Journal of neuroscience : the official journal of the Society for Neuroscience 98 15858067
2010 P-Rex1 participates in Neuregulin-ErbB signal transduction and its expression correlates with patient outcome in breast cancer. Oncogene 81 21042280
2014 P-REX1 creates a positive feedback loop to activate growth factor receptor, PI3K/AKT and MEK/ERK signaling in breast cancer. Oncogene 78 25284585
2007 Membrane translocation of P-Rex1 is mediated by G protein betagamma subunits and phosphoinositide 3-kinase. The Journal of biological chemistry 73 17698854
2010 P-Rex1 and Vav1 cooperate in the regulation of formyl-methionyl-leucyl-phenylalanine-dependent neutrophil responses. Journal of immunology (Baltimore, Md. : 1950) 70 21178006
2015 Synaptic P-Rex1 signaling regulates hippocampal long-term depression and autism-like social behavior. Proceedings of the National Academy of Sciences of the United States of America 62 26621702
2014 P-Rex1 directly activates RhoG to regulate GPCR-driven Rac signalling and actin polarity in neutrophils. Journal of cell science 59 24659802
2009 Phosphatidylinositol 3,4,5-triphosphate-dependent Rac exchanger 1 (P-Rex-1), a guanine nucleotide exchange factor for Rac, mediates angiogenic responses to stromal cell-derived factor-1/chemokine stromal cell derived factor-1 (SDF-1/CXCL-12) linked to Rac activation, endothelial cell migration, and in vitro angiogenesis. Molecular pharmacology 59 20018810
2011 Identification of P-Rex1 as a novel Rac1-guanine nucleotide exchange factor (GEF) that promotes actin remodeling and GLUT4 protein trafficking in adipocytes. The Journal of biological chemistry 58 22002247
2016 P-Rex1 Promotes Resistance to VEGF/VEGFR-Targeted Therapy in Prostate Cancer. Cell reports 52 26923603
2015 The Phosphatidylinositol (3,4,5)-Trisphosphate-dependent Rac Exchanger 1·Ras-related C3 Botulinum Toxin Substrate 1 (P-Rex1·Rac1) Complex Reveals the Basis of Rac1 Activation in Breast Cancer Cells. The Journal of biological chemistry 52 26112412
2012 Nodal signaling regulates endodermal cell motility and actin dynamics via Rac1 and Prex1. The Journal of cell biology 49 22945937
2005 Phosphorylation of P-Rex1 by the cyclic AMP-dependent protein kinase inhibits the phosphatidylinositiol (3,4,5)-trisphosphate and Gbetagamma-mediated regulation of its activity. The Journal of biological chemistry 48 16301320
2007 Signaling requirements for translocation of P-Rex1, a key Rac2 exchange factor involved in chemoattractant-stimulated human neutrophil function. Journal of leukocyte biology 46 17227822
2008 Domain-domain interaction of P-Rex1 is essential for the activation and inhibition by G protein betagamma subunits and PKA. Cellular signalling 42 18514484
2008 P-Rex1 - a multidomain protein that regulates neurite differentiation. Journal of cell science 42 18697831
2017 P-Rex1 and P-Rex2 RacGEFs and cancer. Biochemical Society transactions 39 28710285
2013 Cucurbitacin I inhibits Rac1 activation in breast cancer cells by a reactive oxygen species-mediated mechanism and independently of Janus tyrosine kinase 2 and P-Rex1. Molecular pharmacology 38 23478800
2005 Differential sensitivity of P-Rex1 to isoforms of G protein betagamma dimers. The Journal of biological chemistry 37 16301321
2016 Protein Kinase A (PKA) Type I Interacts with P-Rex1, a Rac Guanine Nucleotide Exchange Factor: EFFECT ON PKA LOCALIZATION AND P-Rex1 SIGNALING. The Journal of biological chemistry 36 26797121
2010 Analysis of candidate genes on chromosome 20q12-13.1 reveals evidence for BMI mediated association of PREX1 with type 2 diabetes in European Americans. Genomics 36 20650312
2014 Subtype-specific overexpression of the Rac-GEF P-REX1 in breast cancer is associated with promoter hypomethylation. Breast cancer research : BCR 35 25248717
2013 P-Rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments. PloS one 32 23382862
2019 Cryo-electron microscopy structure and analysis of the P-Rex1-Gβγ signaling scaffold. Science advances 31 31663027
2018 Gβγ signaling to the chemotactic effector P-REX1 and mammalian cell migration is directly regulated by Gαq and Gα13 proteins. The Journal of biological chemistry 31 30446620
2012 The guanine-nucleotide-exchange factor P-Rex1 is activated by protein phosphatase 1α. The Biochemical journal 31 22242915
2018 GRK2 mediates TCR-induced transactivation of CXCR4 and TCR-CXCR4 complex formation that drives PI3Kγ/PREX1 signaling and T cell cytokine secretion. The Journal of biological chemistry 30 30018141
2016 ERK/MAPK Signaling Drives Overexpression of the Rac-GEF, PREX1, in BRAF- and NRAS-Mutant Melanoma. Molecular cancer research : MCR 29 27418645
2019 PREX1 drives spontaneous bone dissemination of ER+ breast cancer cells. Oncogene 28 31636389
2016 PtdIns(3,4,5)P3-dependent Rac Exchanger 1 (PREX1) Rac-Guanine Nucleotide Exchange Factor (GEF) Activity Promotes Breast Cancer Cell Proliferation and Tumor Growth via Activation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) Signaling. The Journal of biological chemistry 27 27358402
2024 Heterogeneity-induced NGF-NGFR communication inefficiency promotes mitotic spindle disorganization in exhausted T cells through PREX1 suppression to impair the anti-tumor immunotherapy with PD-1 mAb in hepatocellular carcinoma. Cancer medicine 26 38204220
2016 Norbin Stimulates the Catalytic Activity and Plasma Membrane Localization of the Guanine-Nucleotide Exchange Factor P-Rex1. The Journal of biological chemistry 26 26792863
2009 Sphingosine-1-phosphate receptor S1P1 is regulated by direct interactions with P-Rex1, a Rac guanine nucleotide exchange factor. Biochemical and biophysical research communications 24 20036214
2020 Discovery of Small Molecules That Target the Phosphatidylinositol (3,4,5) Trisphosphate (PIP3)-Dependent Rac Exchanger 1 (P-Rex1) PIP3-Binding Site and Inhibit P-Rex1-Dependent Functions in Neutrophils. Molecular pharmacology 22 31900312
2018 cAMP-dependent activation of the Rac guanine exchange factor P-REX1 by type I protein kinase A (PKA) regulatory subunits. The Journal of biological chemistry 22 30530493
2016 PREX1 Protein Function Is Negatively Regulated Downstream of Receptor Tyrosine Kinase Activation by p21-activated Kinases (PAKs). The Journal of biological chemistry 22 27481946
2017 PREX1 integrates G protein-coupled receptor and phosphoinositide 3-kinase signaling to promote glioblastoma invasion. Oncotarget 20 28051998
2017 TCR-CXCR4 signaling stabilizes cytokine mRNA transcripts via a PREX1-Rac1 pathway: implications for CTCL. Blood 20 28694325
2013 Phosphorylation of P-Rex1 at serine 1169 participates in IGF-1R signaling in breast cancer cells. Cellular signalling 20 23899556
2020 PtdIns(3,4,5)P3-dependent Rac exchanger 1 (P-Rex1) promotes mammary tumor initiation and metastasis. Proceedings of the National Academy of Sciences of the United States of America 19 33097662
2016 Identification of P-Rex1 as an anti-inflammatory and anti-fibrogenic target for pulmonary fibrosis. Scientific reports 19 27173636
2017 P-REX1 amplification promotes progression of cutaneous melanoma via the PAK1/P38/MMP-2 pathway. Cancer letters 18 28803992
2010 Characterization of P-Rex1 for its role in fMet-Leu-Phe-induced superoxide production in reconstituted COS(phox) cells. Cellular signalling 18 20074642
2008 Lack of a significant role of P-Rex1, a major regulator of macrophage Rac1 activation and chemotaxis, in atherogenesis. Prostaglandins & other lipid mediators 18 18502673
2011 Characterization of the Rac guanine nucleotide exchange factor P-Rex1 in platelets. Journal of molecular signaling 17 21884615
2020 The first DEP domain of the RhoGEF P-Rex1 autoinhibits activity and contributes to membrane binding. The Journal of biological chemistry 16 32661198
2020 P-REX1-Independent, Calcium-Dependent RAC1 Hyperactivation in Prostate Cancer. Cancers 15 32092966
2006 Purification of P-Rex1 from neutrophils and nucleotide exchange assay. Methods in enzymology 15 16472647
2019 P-Rex1 Overexpression Results in Aberrant Neuronal Polarity and Psychosis-Related Behaviors. Neuroscience bulletin 14 31286410
2023 The pseudokinase NRBP1 activates Rac1/Cdc42 via P-Rex1 to drive oncogenic signalling in triple-negative breast cancer. Oncogene 13 36693952
2020 P-Rex1 Mediates Glucose-Stimulated Rac1 Activation and Insulin Secretion in Pancreatic β-Cells. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 13 33347743
2016 Characterization of a P-Rex1 gene signature in breast cancer cells. Oncotarget 13 27351228
2016 The P-Rex1/Rac signaling pathway as a point of convergence for HER/ErbB receptor and GPCR responses. Small GTPases 13 27588611
2017 P-Rex1 Expression in Invasive Breast Cancer in relation to Receptor Status and Distant Metastatic Site. International journal of breast cancer 12 28698809
2016 Multisite phosphorylation of P-Rex1 by protein kinase C. Oncotarget 12 27788493
2020 Identification of P-Rex1 in the Regulation of Liver Cancer Cell Proliferation and Migration via HGF/c-Met/Akt Pathway. OncoTargets and therapy 11 33061433
2018 P-Rex1 is dispensable for Erk activation and mitogenesis in breast cancer. Oncotarget 11 29983884
2024 PREX1 improves homeostatic proliferation to maintain a naive CD4+ T cell compartment in older age. JCI insight 9 38329813
2022 PREX1 depletion ameliorates high-fat diet-induced non-alcoholic fatty liver disease in mice and mitigates palmitic acid-induced hepatocellular injury via suppressing the NF-κB signaling pathway. Toxicology and applied pharmacology 9 35605788
2023 Paeoniflorin shows chondroprotective effects under IL-1β stress by regulating circ-PREX1/miR-140-3p/WNT5B axis. Journal of orthopaedic surgery and research 8 37817257
2021 Gβγ recruits and activates P-Rex1 via two independent binding interfaces. Biochemical and biophysical research communications 8 33412417
2020 The Rho guanine nucleotide exchange factor P-Rex1 as a potential drug target for cancer metastasis and inflammatory diseases. Pharmacological research 8 32006571
2015 The PREX1/Rac signaling axis: Potential as a biomarker and therapeutic target in breast cancer. Molecular & cellular oncology 8 27308485
2021 P-Rex1 Controls Sphingosine 1-Phosphate Receptor Signalling, Morphology, and Cell-Cycle Progression in Neuronal Cells. Cells 7 34572121
2011 P-Rex1, a guanine exchange factor that is overexpressed in breast cancer, is a convergence node for ErbB and CXCR4 signaling. Molecular cell 7 21211718
2024 ∆Np63α inhibits Rac1 activation and cancer cell invasion through suppression of PREX1. Cell death discovery 6 38191532
2023 Silencing Rac1 and Prex1 Inhibit Epithelial-Mesenchymal Transition in Human Gastric Cancer Cells Induced by Transforming Growth Factor-β1. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 6 37434402
2023 P-Rex1 is a novel substrate of the E3 ubiquitin ligase Malin associated with Lafora disease. Neurobiology of disease 5 36638890
2024 Structural and dynamic changes in P-Rex1 upon activation by PIP3 and inhibition by IP4. eLife 4 39082940
2023 Structural Dynamics of P-Rex1 Complexed with Natural Leads Establishes the Protein as an Attractive Target for Therapeutics to Suppress Cancer Metastasis. BioMed research international 4 38098889
2022 P-Rex1 Signaling Hub in Lower Grade Glioma Patients, Found by In Silico Data Mining, Correlates With Reduced Survival and Augmented Immune Tumor Microenvironment. Frontiers in oncology 4 35875157
2025 P-Rex1 limits glucose clearance and suppresses hepatocyte glucose uptake and mitochondrial metabolism independently of its Rac-GEF activity. Cell reports 3 41046518
2024 Migration, invasion, and metastasis are mediated by P-Rex1 in neuroblastoma. Frontiers in oncology 3 38884093
2026 P-Rex2 exhibits unique structural features and regulatory mechanisms distinct from the closely related RhoGEF P-Rex1. bioRxiv : the preprint server for biology 2 41542420
2025 P-Rex1 controls phagocytosis and the killing of bacteria by murine neutrophils independently of its catalytic activity. Frontiers in immunology 2 41098722
2025 P-Rex1 limits the agonist-induced internalization of GPCRs independently of its Rac-GEF activity. Cell reports 2 41100251
2023 Pharmacological Inhibition of P-Rex1/Rac1 Axis Blocked Angiotensin II-Induced Cardiac Fibrosis. Cardiovascular drugs and therapy 2 36892683
2021 P-Rex1 Cooperates With TGFβR2 to Drive Lung Fibroblast Migration in Pulmonary Fibrosis. Frontiers in pharmacology 2 34349645
2025 Upregulation of PREX1 Expression by POU2F2 Promotes the Malignant Progression of Acute Myeloid Leukemia via the mTOR Pathway. Journal of biochemical and molecular toxicology 1 40317800
2025 Inhibition of PREX1 Reverses Enzalutamide Resistance in Castration-Resistant Prostate Cancer. The world journal of men's health 1 41508386
2026 Endocrine therapy reprogramming of breast cancer facilitates metastatic escape via upregulation of P-Rex1/Rac1 signalling. Nature communications 0 42115169
2026 The Rho guanine-nucleotide exchange factor P-Rex2 exhibits structural and regulatory features distinct from the related RhoGEF P-Rex1. The Journal of biological chemistry 0 42248461
2024 Structural and dynamic changes in P-Rex1 upon activation by PIP3 and inhibition by IP4. bioRxiv : the preprint server for biology 0 37745379

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