Affinage

RAC2

Ras-related C3 botulinum toxin substrate 2 · UniProt P15153

Length
192 aa
Mass
21.4 kDa
Annotated
2026-06-10
100 papers in source corpus 49 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

RAC2 is a hematopoietic Rho-family GTPase that cycles between GDP- and GTP-bound states to control the actin cytoskeleton, NADPH oxidase-dependent superoxide production, and immune-cell effector functions (PMID:10072071, PMID:14564009, PMID:12391220). It is essential for chemoattractant- and FcγR-driven neutrophil chemotaxis, F-actin generation, MAP kinase activation, primary (azurophilic) granule exocytosis, and respiratory burst, and its loss is not compensated by elevated Rac1, demonstrating non-redundant signaling (PMID:10072071, PMID:11145705, PMID:15073033, PMID:12391220). As a component of the respiratory burst oxidase, activated RAC2 translocates from cytosol to the submembranous/phagosomal membrane and assembles with the gp91phox–p47phox–p67phox complex, with phosphorylation of gp91phox by PKC enhancing its binding to RAC2 and the cytosolic phox subunits (PMID:8120032, PMID:8670049, PMID:19028840). RAC2 routes distinct effectors through separable interfaces: ARP2/3-dependent de novo nucleation and cofilin-dependent severing for actin free barbed-end generation, PAK1/p67phox for superoxide, PLCβ2 for local PIP2 hydrolysis at the membrane, and Myosin IIA (Myh9) for mRNA-stabilizing signaling, such that effector-domain mutants can dissociate superoxide production from chemotaxis (PMID:15814684, PMID:17954607, PMID:12509427, PMID:25180062). Membrane targeting and function require C-terminal geranylgeranylation at the CAAX cysteine and the adjacent TRQQKRP motif (PMID:1903399, PMID:12176888). Beyond the myeloid compartment, RAC2 drives TH1 IFN-γ production via NF-κB/p38, mast-cell survival via Akt/BAD/Bcl-XL, and B-cell adhesion to ICAM-1 and immunological synapse formation (PMID:10864872, PMID:10843388, PMID:18191593). Its nucleotide cycle is set by multiple GEFs including P-Rex1, DOCK2, and PLD2 (PMID:16243036, PMID:12176041, PMID:22106281). Distinct human primary immunodeficiencies arise from RAC2 mutations: the dominant-negative D57N allele blocks GTP binding and sequesters GEFs, while gain-of-function alleles such as E62K impair GAP-accelerated hydrolysis to yield constitutive activity, with a broader allelic series producing SCID-, LAD-, and CID-like phenotypes (PMID:10758162, PMID:10961859, PMID:11278678, PMID:30723080, PMID:38194689).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1991 High

    Established how RAC2 achieves membrane association by defining its C-terminal lipid modification, a prerequisite for any membrane-localized GTPase function.

    Evidence In vitro translation with radiolabeled isoprenoid precursors and CAAX-motif mutagenesis

    PMID:1903399

    Open questions at the time
    • Did not link prenylation to a specific cellular function
    • Prenyltransferase responsible not identified in this study
  2. 1994 High

    Placed RAC2 in the respiratory burst oxidase by showing activation-dependent translocation to the actin-associated membrane fraction, defining its assembly behavior with phox subunits.

    Evidence Subcellular fractionation of normal and p47phox-deficient neutrophils with immunoblotting

    PMID:8120032

    Open questions at the time
    • p47phox-dependence of translocation later contradicted by CGD-patient fractionation (#19)
    • Direct binding interfaces not mapped here
  3. 1997 High

    Defined the biochemical nucleotide cycle of RAC2, showing activating mutations resist GAP-accelerated hydrolysis and that GEF action requires intact switch regions.

    Evidence In vitro GTP hydrolysis and GAP/GEF assays with purified recombinant RAC2 mutants

    PMID:9012677

    Open questions at the time
    • Physiological GAPs/GEFs in hematopoietic cells not identified
    • No cellular phenotype linked to these mutants
  4. 1999 High

    Demonstrated that RAC2 is an essential, non-redundant regulator of multiple specialized neutrophil functions in vivo, moving it from biochemistry to organismal immunity.

    Evidence Rac2 knockout mouse with chemotaxis, F-actin, MAPK, superoxide, and infection-challenge assays

    PMID:10072071

    Open questions at the time
    • Did not resolve which effector pathways mediate each defect
    • Did not distinguish RAC2- from RAC1-specific contributions
  5. 1999 High

    Identified the upstream signaling that loads RAC2 with GTP, separating PI3K/Gi-dependent receptor activation from PI3K-independent PMA activation.

    Evidence PAK-RBD pulldown of RAC2-GTP in human neutrophils with pharmacological inhibitors

    PMID:10364257

    Open questions at the time
    • Specific GEFs downstream of PI3K not identified
    • Mechanism of PMA/PI3K-independent activation undefined
  6. 2000 High

    Linked RAC2 to human disease by showing the dominant-negative D57N allele causes neutrophil immunodeficiency through loss of GTP binding and GEF sequestration.

    Evidence Patient analysis, in vitro NADPH oxidase reconstitution, GTP-binding kinetics, and bone marrow transduction

    PMID:10758162 PMID:10961859 PMID:11278678

    Open questions at the time
    • How D57N sequesters GEFs to suppress Rac1 not structurally resolved
    • Did not address gain-of-function disease alleles
  7. 2000 High

    Extended RAC2 function beyond neutrophils, establishing non-redundant survival signaling in mast cells and TH1-specific IFN-γ transcription.

    Evidence Rac2 KO mast cells (Akt/BAD/Bcl-XL) and KO/gain-of-function T cells with IFN-γ promoter reporters

    PMID:10843388 PMID:10864872

    Open questions at the time
    • Direct effectors linking RAC2 to Akt and to NF-κB/p38 not identified
    • Cell-type basis of TH1-restricted expression unexplained
  8. 2001 High

    Resolved the stimulus-specificity of RAC2-dependent oxidase activation and connected RAC2 to ERK/p38 signaling and to NF1-pathway crosstalk in mast cells.

    Evidence Rac2 KO neutrophils across multiple agonists; Nf1+/- × Rac2-/- genetic intercross with ERK assays

    PMID:11145705 PMID:11435472

    Open questions at the time
    • Why opsonized zymosan response is RAC2-independent unexplained
    • Direct biochemical link between RAC2 and Ras-ERK not defined
  9. 2002 Medium

    Quantified preferential RAC2 activation over RAC1 and defined parallel upstream GEF pathways (PI3K and Src-ELMO-DOCK2) converging on RAC2.

    Evidence PAK-RBD pulldowns in KO neutrophils; pharmacological/genetic epistasis with DOCK2 knockdown and Src-family triple-KO cells

    PMID:12176041 PMID:12391220 PMID:18662984

    Open questions at the time
    • Molecular basis of RAC2-vs-RAC1 GEF preference unresolved
    • DOCK2-CD3ζ link rests on Co-IP plus reporter without reciprocal validation
  10. 2002 Medium

    Connected RAC2 membrane targeting to function and identified PLCβ2 as a membrane-localized effector controlled by RAC2.

    Evidence TRQQKRP deletion mutagenesis with prenylation/rescue assays; FRAP of GFP-PLCβ2 with constitutively active RAC2

    PMID:12176888 PMID:12509427

    Open questions at the time
    • Direct RAC2-PLCβ2 binding interface not mapped
    • Physiological setting of RAC2-PLCβ2 signaling in immune cells untested
  11. 2003 High

    Defined the genetic division of labor between RAC1 and RAC2 in hematopoiesis and clarified component-specific oxidase translocation requirements.

    Evidence Rac1/Rac2 double-KO mice; CGD-patient fractionation distinguishing translocation dependencies; Rac2 KO macrophage host-defense assays

    PMID:14564009 PMID:15528331 PMID:8670049

    Open questions at the time
    • Molecular basis for distinct RAC1/RAC2 outputs from shared effectors unresolved
    • RAC2 translocation mechanism (GEF/membrane recruitment) undefined
  12. 2004 High

    Resolved the spatiotemporal dynamics of RAC2 during phagocytosis and identified primary-granule exocytosis as a RAC2-dependent process.

    Evidence FRET and FRAP live-imaging of GFP/PAK-PBD chimeras during phagocytosis; Rac2 KO granule-release and CD63-mobilization assays

    PMID:14623873 PMID:15073033 PMID:15169870

    Open questions at the time
    • Effectors mediating granule mobilization not identified
    • Mechanism of dynamic phagosome exchange unexplained
  13. 2005 High

    Dissected RAC2 effector specificity, showing superoxide and chemotaxis run through separable effector interfaces, and identified RAC2-binding partners that regulate oxidase activity.

    Evidence Systematic effector-domain mutants with rescue assays in Rac2-/- neutrophils; S100A8/A9 and arachidonic-acid bypass studies

    PMID:15642721 PMID:15814684 PMID:16275890

    Open questions at the time
    • How RAC2 contributes to assembled-oxidase activity beyond assembly remains partly defined by bypass only
    • Structural basis of effector selectivity not solved
  14. 2007 High

    Mechanistically separated RAC2-driven actin barbed-end generation (cofilin severing plus ARP2/3 nucleation) from RAC1-mediated uncapping.

    Evidence Free barbed-end assays in permeabilized Rac1-/- and Rac2-/- neutrophils with cofilin/ARP2/3 inhibitors

    PMID:17954607

    Open questions at the time
    • Direct biochemical link from RAC2 to cofilin not established
    • How RAC2 selects nucleation over uncapping unknown
  15. 2008 High

    Identified P-Rex1 as a RAC2-preferential GEF and established RAC2 as the BCR-driven GTPase required for B-cell adhesion and immunological synapse formation.

    Evidence P-Rex1 KO neutrophils with GEF-preference Co-IP; Rac2 KO B cells with Rap1-GTP, ICAM-1 adhesion, and IS imaging

    PMID:16243036 PMID:18191593

    Open questions at the time
    • Structural basis of P-Rex1 RAC2 selectivity unresolved
    • Link between RAC2 and Rap1-GTP not mechanistically defined
  16. 2008 High

    Showed PKC phosphorylation of gp91phox/NOX2 enhances RAC2 and phox-subunit binding, providing a regulatory node for oxidase assembly.

    Evidence In vitro PKC phosphorylation of recombinant gp91phox with binding and peptide-mapping assays

    PMID:19028840

    Open questions at the time
    • In vivo contribution of this phosphorylation to RAC2 recruitment untested
    • Phosphosite-to-binding causality not isolated
  17. 2011 High

    Identified PLD2 as a direct catalytic-independent GEF for RAC2 with reciprocal negative feedback, and expanded RAC2 roles into in vivo motility, mitochondrial ROS, and effector-triggered immunity.

    Evidence In vitro GEF assays/FRET/CRIB-domain mutagenesis for PLD2; zebrafish Rac2 morphants; CML mitochondrial-ROS models; CNF1-IMD/Rip co-IP

    PMID:21378159 PMID:22014524 PMID:22018470 PMID:22106281 PMID:22411871

    Open questions at the time
    • Physiological dominance of PLD2 vs other GEFs in vivo unresolved
    • Mechanism by which RAC2 alters complex-III electron flow undefined
    • CNF1-modified RAC2 adaptor interactions rest on Co-IP
  18. 2013 Medium

    Extended RAC2 effector repertoire to iNOS and Myosin IIA, linking RAC2 to combined ROS/RNS microbicidal output and to mRNA-stabilizing monocyte signaling.

    Evidence Reciprocal Co-IP and knockdown for iNOS-RAC2; proteomics/Co-IP for RAC2-Myh9 with myeloid-specific Myh9 KO arteriogenesis model

    PMID:23875749 PMID:25180062

    Open questions at the time
    • iNOS-RAC2 interaction from single-lab Co-IP/knockdown
    • How RAC2-Myh9 drives HuR translocation mechanistically undefined
  19. 2016 Medium

    Implicated RAC2 in disease contexts beyond immunodeficiency, including ibrutinib-resistant CLL via PLCγ2, atherosclerotic calcification, and dendritic-cell cross-presentation.

    Evidence PLCγ2 mutant Ca2+ flux with Rac inhibitor/Rac-resistance mutation; Rac2 KO atherogenesis; WASp-deficient DC phagosomal pH assays

    PMID:27425374 PMID:27542411 PMID:27834690

    Open questions at the time
    • Each mechanism rests on single-lab pharmacology/KO without independent confirmation
    • Direct RAC2-PLCγ2 binding in CLL cells not shown
    • RAC2 suppression of Rac1-IL-1β mechanistically incomplete
  20. 2019 High

    Defined the gain-of-function disease mechanism: RAC2 E62K resists GAP-accelerated hydrolysis to give prolonged GTP loading, excessive superoxide, and lymphopenia.

    Evidence Patient cells, GTP-hydrolysis/GAP-responsiveness biochemistry, and Rac2+/E62K knock-in mice

    PMID:30723080

    Open questions at the time
    • How constitutive RAC2 activity produces T/B lymphopenia not fully mechanistic
    • Tissue-specific consequences of GOF signaling incomplete
  21. 2022 High

    Identified post-translational control of RAC2 abundance via ALDH2-mediated protection from K48 ubiquitination, linking RAC2 stability to macrophage efferocytosis.

    Evidence Co-IP, K48-ubiquitination analysis, ALDH2 KO/rescue macrophages, and human rs671-carrier efferocytosis assays

    PMID:35354308

    Open questions at the time
    • E3 ligase targeting RAC2 K123 not identified
    • Whether RAC2 stability is broadly regulated this way in other lineages untested
  22. 2024 High

    Comprehensively mapped the RAC2 allelic series to distinct immunodeficiency phenotypes and added context-specific roles in cancer and mechanotransduction.

    Evidence Functional characterization of 23 RAC2 mutations across superoxide/PAK1/AKT/stability assays in 54 patients; MUC21-RAC2 axis in PDAC; RAC2 mechanotransduction in FBR model

    PMID:37749310 PMID:38194689 PMID:39020072

    Open questions at the time
    • Genotype-phenotype rules for intermediate alleles incompletely predictive
    • MUC21-RAC2 and mechanotransduction mechanisms rest on single-lab evidence

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct GEFs, GAPs, effector interfaces, and post-translational modifications are integrated to produce RAC2's cell-type- and stimulus-specific outputs, and to explain why specific mutations yield SCID-, LAD-, versus CID-like disease, remains unresolved.
  • No structural model explaining RAC2 vs RAC1 effector/GEF discrimination
  • Quantitative rules linking GTP-loading levels to specific disease phenotypes lacking
  • In vivo hierarchy among P-Rex1, DOCK2, and PLD2 GEFs undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0003924 GTPase activity 3 GO:0060089 molecular transducer activity 3 GO:0008092 cytoskeletal protein binding 2
Localization
GO:0005829 cytosol 3 GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2 GO:0031410 cytoplasmic vesicle 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-8953897 Cellular responses to stimuli 3
Partners
DOCK2INOSMYH9P-REX1P67PHOXPAK1PLCB2PLD2
Complex memberships
NADPH oxidase (NOX2/gp91phox-p47phox-p67phox)

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 Rac2 deficiency in mice causes significant defects in neutrophil chemotaxis, shear-dependent L-selectin-mediated capture on Glycam-1, F-actin generation, p38 and p42/p44 MAP kinase activation induced by chemoattractants, and reduced superoxide production in bone marrow neutrophils, establishing Rac2 as an essential regulator of multiple specialized neutrophil functions. Rac2 knockout mouse model with functional assays (chemotaxis, F-actin generation, MAPK activation, superoxide production, in vivo infection challenge) Immunity High 10072071
1994 Rac2 functions as a component of the neutrophil respiratory burst oxidase; upon neutrophil activation, Rac2 (along with p47phox and p67phox) translocates from cytosol to the submembranous actin cytoskeleton. Rac2 translocation to the membrane was not observed in p47phox-deficient neutrophils, indicating Rac2 transfer depends on p47phox. Subcellular fractionation of activated normal and p47phox-deficient neutrophils; Western blot for Rac2, p47phox, p67phox The Journal of biological chemistry High 8120032
1991 Rac2 undergoes carboxyl-terminal isoprenylation with a 20-carbon geranylgeranyl group (not farnesyl), dependent on a cysteine in the fourth position from the carboxyl terminus, which requires the three-amino acid extension distal to the cysteine. In vitro transcription/translation with [3H]mevalonate or [3H]farnesyl pyrophosphate labeling; Raney nickel hydrolysis with gel permeation chromatography; site-directed mutagenesis of CAAX motif The Journal of biological chemistry High 1903399
2000 A dominant-negative Rac2 D57N mutation (Asp57Asn) causes human neutrophil immunodeficiency; Rac2(D57N) binds GDP but not GTP, inhibits oxidase activation and superoxide production in vitro, and addition of recombinant Rac to patient neutrophil extracts reconstitutes O2- production. Patient molecular analysis, Western blot, in vitro NADPH oxidase reconstitution assay, GTP-binding biochemistry Proceedings of the National Academy of Sciences of the United States of America High 10758162 10961859
2000 Rac2(D57N) exhibits markedly enhanced rate of GTP dissociation, ~10% GTP binding ability vs. wild type, does not respond to guanine nucleotide exchange factors, and acts in a dominant-negative fashion by sequestering endogenous GEFs, reducing activity of both Rac2 and Rac1 in cells. In vitro nucleotide binding kinetics with purified recombinant proteins; GEF responsiveness assay; retroviral transduction of bone marrow cells; functional assays (migration, O2- production) The Journal of biological chemistry High 11278678
1999 In human neutrophils, fMLP and LTB4 stimulation of Gi-coupled receptors leads to rapid, transient GTP-loading of Rac2 via a PI3K-dependent pathway (blocked by wortmannin/LY294002 and pertussis toxin), while PMA activates Rac2 in a PI3K-independent manner. PAK-RBD pulldown assay for Rac2-GTP in human neutrophils; pharmacological inhibitors (wortmannin, LY294002, pertussis toxin) The Journal of biological chemistry High 10364257
2003 Deletion of both Rac1 and Rac2 murine alleles leads to massive egress of hematopoietic stem/progenitor cells into blood from marrow, while Rac1 (not Rac2) regulates HSC/P engraftment. Rac2 (not Rac1) regulates superoxide production and directed migration in neutrophils; both GTPases have distinct roles in actin organization, cell survival, and proliferation. Conditional/constitutive double knockout mice; bone marrow transplantation; functional assays for HSC engraftment, superoxide production, migration, actin organization Science High 14564009
2001 Rac2 is an essential regulator of neutrophil NADPH oxidase activation downstream of chemoattractant (fMLP) and Fcgamma receptors in a stimulus-specific manner; superoxide production in rac2-/- neutrophils is almost absent to fMLP, reduced to 22% for IgG-coated SRBC, but normal for opsonized zymosan. Rac2 deficiency also decreases ERK1/2 and p38 MAP kinase phosphorylation induced by PMA or fMLP. Rac2 knockout mouse neutrophils; superoxide assays with multiple agonists; phospho-kinase Western blots; pharmacological kinase inhibitors Journal of immunology High 11145705
2004 During FcγR-mediated phagocytosis, Rac2 activation increases uniformly and transiently in the actin-poor region of phagosomal membrane during phagosome closure; Rac2 displays a distinct spatial and temporal activation pattern from Rac1 and Cdc42 within phagocytic cups. FRET-based stoichiometry imaging using fluorescent chimeras of Rac2 and PAK1-PBD in macrophages; quantitative live-cell microscopy during phagocytosis Molecular biology of the cell High 15169870
2004 Rac2 is required for primary (azurophilic) granule exocytosis (myeloperoxidase and elastase release) in neutrophils in response to chemoattractants but is not required for secondary/tertiary granule release, and Rac2-deficient neutrophils fail to mobilize CD63+ primary granule marker. Rac2 knockout mouse neutrophils; granule content release assays; confocal microscopy for CD63 mobilization; priming experiments with TNF Blood High 15073033
2000 Rac2 stimulates Akt activation and regulates BAD/Bcl-XL expression in mast cells; Rac2-deficient mast cells show defective adhesion, migration, degranulation, reduced growth factor-induced survival, and lack of Akt activation despite 3-fold induction of Rac1, indicating Rac2 plays a unique non-redundant survival role. Rac2 knockout mouse mast cells; Akt phosphorylation Western blots; BAD/Bcl-XL expression analysis; functional adhesion, migration, degranulation assays Immunity High 10843388
2000 Rac2 activates IFN-γ gene expression in TH1 cells through cooperative activation of NF-κB and p38 MAP kinase pathways; Rac2 is selectively expressed in TH1 (not TH2) cells, and Rac2-/- T cells show decreased IFN-γ production under TH1 conditions. Representational display analysis for Rac2 expression; IFN-γ promoter reporter assay; tetracycline-regulated constitutively active Rac2 transgenic mice; Rac2 knockout T cells Science High 10864872
2005 P-Rex1 (a Gβγ and PIP3-regulated GEF) is a primary GEF for Rac2 (not Rac1) in mouse neutrophils; P-Rex1 deficiency diminishes Rac2-GTP but not Rac1-GTP in response to fMLP. P-Rex1 shows higher affinity for Rac2 than Rac1 as demonstrated by preferential co-immunoprecipitation with dominant-negative Rac2(S17N) vs Rac1(S17N). P-Rex1 knockout mice; affinity precipitation for Rac-GTP; co-immunoprecipitation with dominant-negative GTPases; F-actin formation, superoxide, and chemotaxis assays Current biology High 16243036
2005 Rac2 controls chemotaxis and superoxide production via distinct, separable effector pathways; the N43A mutant (binds Por1/Arfaptin2, p67phox, and Pak1) rescues superoxide but not chemotaxis, while Y40C (defective for all three effectors) rescues neither but rescues myeloid colony growth, demonstrating multiple distinct downstream effector pathways. Structure-function analysis of Rac2 effector domain mutants (V36A, F37A, N39A, N43A, Y40C) expressed in Rac2-/- neutrophils; rescue assays for superoxide, chemotaxis, and colony formation; effector binding assays (Pak1, p67phox, Por1) Journal of immunology High 15814684
2002 The TRQQKRP motif near the C-terminus of Rac2 is essential for efficient geranylgeranylation and correct intracellular localization; deletion of TRQQKRP causes diminished prenylation and delocalization of Rac2, impairing its ability to rescue migration and NADPH oxidase deficiencies in Rac2-deficient cells. Deletion mutagenesis; retroviral expression in Rac2-deficient cells; prenylation analysis; functional rescue assays (migration, NADPH oxidase); fluorescence microscopy for localization Blood High 12176888
1997 Rac2 G12V and Q61L activating mutations hydrolyze GTP very slowly and are unresponsive to p190 Rac-GAP; GEF smgGDS-mediated nucleotide exchange requires intact Switch 1 and Switch 2 regions of Rac2. In vitro GTP hydrolysis assays with purified recombinant Rac2 mutants; GAP responsiveness assay with p190; GEF exchange assays with smgGDS and Switch region mutants Biochemistry High 9012677
2002 Phosphoinositide 3-kinase (PI3K)-dependent and Src-ELMO-Dock2-dependent parallel pathways both converge to activate Rac2 and mediate chemotaxis in neutrophils in response to CXCL8; inhibition of PI3K impairs motility but not chemotaxis, while inhibition of both PI3K and Src severely impairs chemotaxis. Pharmacological inhibitors (wortmannin, PP2); Dock2 shRNA knockdown; hck/fgr/lyn triple-knockout neutrophils; Rac2 activation assays; chemotaxis assays The Journal of biological chemistry Medium 18662984
2002 Rac2 GTP-loading in chemoattractant-stimulated murine neutrophils is ~4-fold greater than Rac1-GTP, and in Rac2-/- neutrophils compensatory Rac1-GTP increases ~3-fold without rescuing F-actin, chemotaxis, or superoxide, demonstrating preferential activation and distinct signaling of Rac2 vs. Rac1. Affinity precipitation for Rac-GTP (PAK-RBD pulldown) in wild-type and rac2-/- neutrophils; F-actin, chemotaxis, and superoxide production assays; Western blot quantification of Rac1/Rac2 levels Journal of immunology High 12391220
2002 DOCK2 associates with the CD3ζ subunit of the TCR complex in T cells and activates Rac2 downstream of TCR stimulation; dominant-negative Rac2 suppresses DOCK2-enhanced IL-2 promoter activity, placing Rac2 downstream of DOCK2 in TCR-mediated IL-2 transcription. Co-immunoprecipitation of DOCK2 with CD3ζ; Rac2 activation assays in 293T cells; stable Jurkat cell transfection; IL-2 promoter-luciferase reporter assays with dominant-negative Rac2 Biochemical and biophysical research communications Medium 12176041
2003 Rac2 (along with p67phox, p47phox, and p40phox) translocates from cytosol to membranes during NADPH oxidase activation; Rac2 translocation is independent of p47phox and p67phox, whereas p40phox and Rac1 translocation depends on p67phox. Subcellular fractionation of neutrophils from CGD patients lacking p67phox or p47phox; Western blotting for NADPH oxidase components The Biochemical journal High 8670049
2003 Rac2 and p67phox continuously exchange between phagosomal membrane and cytosol during phagocytosis, as demonstrated by high FRAP turnover; Rac2 localization to phagosomes does not depend on actin cytoskeleton integrity. GFP-Rac2 and p67-GFP expression in PLB-985 cells; FRAP studies during phagocytosis of serum-treated zymosan; cytochalasin B actin disruption experiments The Journal of biological chemistry Medium 14623873
2002 Constitutively active Rac2(12V) stimulates PLCβ2 activity in live cells and enhances its membrane association; this effect requires the putative N-terminal PH domain of PLCβ2, and Rac2 activity shifts PLCβ2 membrane dynamics from lateral diffusion to exchange with a cytoplasmic pool. FRAP with GFP-PLCβ2 chimeras in live cells; constitutively active Rac2(12V) co-expression; PLCβ2 deletion mutant analysis The Journal of biological chemistry Medium 12509427
2009 Rac2 activation of PLCβ2 leads to interactions with slow-diffusing membrane sites (distinct from Gαq which recruits to fast-diffusing lipid-like components and Gβγ which causes surfing diffusion), establishing Rac2 as directing PLCβ2 to act locally on PIP2 at specific membrane domains. FRAP beam-size analysis combined with biochemical PLCβ2 activation assays; comparison of Gαq, Gβγ, and Rac2 activation in cells expressing GFP-PLCβ2 chimeras The Journal of biological chemistry Medium 20007712
2007 Rac1 and Rac2 regulate actin free barbed end (FBE) generation through distinct mechanisms downstream of fMLP receptor: Rac1 mediates uncapping of existing barbed ends (contributing ~15%), while Rac2 mediates cofilin-dependent severing (~10%) and ARP2/3-dependent de novo nucleation (~75%). Permeabilized neutrophils from Rac1-/- or Rac2-/- mice; free barbed end assays; cofilin and ARP2/3 inhibitor treatments; fMLP receptor signaling maintained The Journal of cell biology High 17954607
2005 S100A8 (component of S100A8/A9 complex) directly binds to p67phox and Rac2, promoting NADPH oxidase activation; S100A8/A9 also transfers arachidonic acid to the NADPH oxidase, and a mutant S100A8/A9 unable to bind arachidonic acid fails to enhance NADPH oxidase activity. Protein-protein interaction studies (pull-down); cell-free NADPH oxidase activation system; S100A9-knockout mouse neutrophils; S100A9-specific antibody inhibition; arachidonic acid binding-mutant S100A8/A9 FASEB journal Medium 15642721
2008 PKC phosphorylates the cytosolic carboxy-terminal flavoprotein domain of gp91phox/NOX2, increasing its diaphorase activity and its binding to Rac2, p67phox, and p47phox, establishing gp91phox phosphorylation as a mechanism of NADPH oxidase regulation. In vitro PKC phosphorylation of recombinant gp91phox; two-dimensional tryptic peptide mapping; binding assays for Rac2/p67phox/p47phox to phosphorylated vs. non-phosphorylated gp91phox; PKC inhibitor studies in intact neutrophils FASEB journal High 19028840
2008 BCR engagement activates Rac2 (and Rac1) via Src-family kinases, Vav1/Vav2 GEFs, and PI3K; Rac2 (not Rac1) is specifically required for B cell adhesion to ICAM-1 and immunological synapse formation; Rac2-deficient B cells show lower Rap1-GTP and severe actin polymerization defects. Rac2-/- primary B cells; Rac2-GTP pulldown assays; pharmacological inhibitors of Src, PI3K; ICAM-1 adhesion assays; IS formation imaging; Rap1-GTP assay; constitutively active Rac2 Immunity High 18191593
2011 PLD2 directly binds Rac2 via two CRIB (Cdc42/Rac-interactive binding) motifs in its PH domain (CRIB-1 and CRIB-2), functioning as a GEF for Rac2 by promoting GDP dissociation (~72% decrease) and GTP association (~300% increase); this interaction requires residue N17 in the Switch-1 region of Rac2 and residues 263-266 in the PH domain of PLD2. Rac2-GTP accumulation provides negative feedback to inhibit PLD2. Co-immunoprecipitation; FRET with CFP-Rac2/YFP-PLD2 chimeras in living cells; in vitro GEF assay with purified recombinant proteins; saturable binding with Kd ~3 nM; deletion mutant analysis; PLD2 catalytically inactive mutant (K758R) retains GEF activity; silencing PLD2 reduces Rac2 activity in cells Proceedings of the National Academy of Sciences of the United States of America High 22106281
2011 PLD2 contains two CRIB domains (CRIB-1 and CRIB-2) in and around the PH domain that specifically bind Rac2; PLD2 binds Rac2-GTP more efficiently than Rac2-GDP or Rac2-N17; increasing concentrations of Rac2 in vitro inhibit PLD2 activity, while Rac2 activity is increased by PLD2-WT but not PLD2-ΔCRIB. Co-immunoprecipitation; FRET; in vitro binding with affinity-purified recombinant proteins (apparent Kd 3 nM); PLD2-ΔCRIB deletion mutants; nucleotide-state-dependent binding assays The Journal of biological chemistry High 21378159
2012 Rac2 GTPase alters mitochondrial membrane potential and electron flow through mitochondrial respiratory chain complex III (MRC-cIII), generating elevated ROS in CML stem cells; genetic deletion or pharmacological inhibition of Rac2 reduces MRC-cIII-generated ROS and consequently reduces genomic instability and chromosomal aberrations. Rac2 genetic deletion in CML mouse models; mitochondrial ROS measurement; MRC-cIII inhibition; mitochondria-targeted catalase/peptide aptamer; chromosomal aberration analysis Blood Medium 22411871
2011 CNF1 (E. coli effector) modifies Rac2, and modified Rac2 then interacts with innate immune adaptors IMD (Drosophila) and Rip1-Rip2 (mammalian cells) to drive a protective immune response, defining a mechanism of effector-triggered immunity. CNF1 modification assay; Co-immunoprecipitation of modified Rac2 with IMD/Rip1-Rip2; infection protection assays in flies and mammalian cells Immunity Medium 22018470
2013 iNOS interacts with Rac2 in the cytosol of resting human neutrophils; the iNOS-Rac2 complex translocates to phagosomes after phagocytosis, where it contributes to superoxide, NO, and ROS/RNS generation and microbial killing. Rac2 silencing reduces iNOS-mediated NO and ROS generation. Co-immunoprecipitation of iNOS with Rac2; subcellular fractionation; siRNA knockdown of Rac2 in human neutrophils; iNOS knockout mice; fluorescent superoxide/NO detection Antioxidants & redox signaling Medium 23875749
2016 PLCγ2 mutants R665W and L845F (found in ibrutinib-resistant CLL) are hypersensitive to activation by wild-type Rac2; their enhanced 'basal' PLCγ2 activity is shown to be Rac2-driven (inhibited by Rac inhibitor EHT 1864 and by PLCγ2-F897Q Rac-resistance mutation), not constitutive, demonstrating Rac2 as the driver of ibrutinib resistance phenotype. PLCγ2 mutant transfection into intact cells; pharmacological Rac inhibitor (EHT 1864); Rac-resistant PLCγ2 mutation (F897Q); Ca2+ flux assays; BCR stimulation The Journal of biological chemistry Medium 27542411
2014 CCR2+β2 integrin co-engagement in monocytes activates Rac2, leading to Rac2-Myosin IIA (Myh9) interaction; this interaction drives nuclear-to-cytosolic HuR translocation and VEGF-A mRNA stabilization. Rac2-Myh9 interaction was identified by proteomics and confirmed biochemically; myeloid-specific Myh9 knockout impairs arteriogenesis. Proteomic analysis for Rac2 interactors; co-immunoprecipitation of Rac2 with Myh9; HuR translocation assay; VEGF-A mRNA stability; myeloid-specific Myh9 knockout mice; hindlimb ischemia model The Journal of experimental medicine High 25180062
2011 Rac2 deficiency in zebrafish impairs 3D neutrophil motility, F-actin polarity, and PI(3)K signaling in vivo; additionally, Rac2 signaling is required for CXCR4-mediated neutrophil retention in hematopoietic tissue, with constitutively active CXCR4 retention (WHIM syndrome model) partially rescued by inhibitory Rac2D57N mutation. Zebrafish Rac2 morphants and Rac2D57N transgenic larvae; noninvasive live imaging; photoconversion tracking of neutrophils; PI(3)K reporter imaging; F-actin polarity measurement Developmental cell High 22014524
2003 In Rac2-/- macrophages, FcγR-mediated phagocytosis and NADPH oxidase activity are significantly decreased while serum-opsonized zymosan-stimulated phagocytosis and oxidant production are normal; Rac2 (minor isoform in macrophages) plays a nonoverlapping role with Rac1 in FcγR-dependent host defense. Rac2 knockout mouse macrophages; FcγR phagocytosis assay; NADPH oxidase activity; peritoneal exudate macrophage accumulation; actin polymerization assays Journal of immunology High 15528331
2003 Macrophage α4β1 and αvβ3/αvβ5 integrin-directed migration specifically requires Rac2 (not Rac1); Syk kinase expression in COS7 cells converts α4β1 migration to Rac2-dependence, suggesting Syk encodes a Rac2-specific signaling axis in myeloid cells. Reconstitution of Rac2 in Rac2-/- macrophages rescues integrin-dependent migration. Rac2 knockout macrophages; retroviral Rac2 reconstitution; COS7 Syk transfection; GTP-Rac2 activation by specific integrins; migration assays on vitronectin and FN-H296 The Journal of biological chemistry Medium 12917394
2011 NCF2 gene product p67phox rare variant (found in VEO-IBD patients) shows reduced binding to RAC2, functionally impairing NADPH oxidase activity. Direct sequencing; functional binding assay of variant p67phox to RAC2; cell-free NADPH oxidase assay Gut Medium 21900546
2019 De novo RAC2[E62K] mutation causes gain-of-function characteristics: GTPase-activating protein fails to accelerate GTP hydrolysis on E62K (while intrinsic hydrolysis is retained), resulting in prolonged GTP-bound RAC2 and excessive superoxide production, impaired fMLP-directed chemotaxis, and abnormal macropinocytosis. Rac2+/E62K mice phenocopy the human T- and B-cell lymphopenia. Patient cells functional assays; cell line transfection with RAC2[E62K]; biochemical GTP hydrolysis and GAP responsiveness assays; Rac2+/E62K knock-in mice; F-actin, superoxide, macropinocytosis assays Blood High 30723080
2022 ALDH2 directly interacts with Rac2 protein and stabilizes it by reducing K48-linked polyubiquitination at lysine 123 of Rac2, preventing its proteasomal degradation; the ALDH2 rs671 mutant fails to stabilize Rac2, impairing macrophage efferocytosis. Rac2 is specifically required for the internalization step of efferocytosis. Co-immunoprecipitation of ALDH2 with Rac2; ubiquitination analysis (K48-specific); ALDH2 knockout mouse macrophages; ALDH2 rescue experiments; RNA-seq and proteomics; efferocytosis assays in human macrophages from rs671 carriers Arteriosclerosis, thrombosis, and vascular biology High 35354308
2016 Rac2 prevents progressive atherosclerotic calcification by suppressing Rac1-dependent macrophage IL-1β expression; Rac2-/- macrophages show increased Rac1-dependent IL-1β, which drives vascular smooth muscle cell osteogenic programs and calcium deposition. Rac2-/- mouse atherogenesis model; macrophage IL-1β expression assays; VSMC calcium deposition assay; Rac1-specific activation assays; human coronary artery samples for Rac2/IL-1β correlation Arteriosclerosis, thrombosis, and vascular biology Medium 27834690
2010 Rac2 GTPase deficiency (but not Rac1) in BCR-ABL+ leukemic stem cells impairs oncogene-induced proliferation and survival signals in vivo, causing functional exhaustion of the leukemic stem cell pool without affecting normal hematopoietic microenvironment interactions (adhesion, migration, homing unaffected). Scl/p210-BCR-ABL binary transgenic mice crossed with Rac2-/- mice; LSC apoptosis and proliferation assays; adhesion/migration/homing assays Blood Medium 20407032
2001 Rac2 mediates cross-talk between PI-3K and the p21ras-Raf-Mek-ERK pathway in NF1-deficient mast cells; genetic intercross of Nf1+/- and Rac2-/- mice shows Rac2 deficiency normalizes hyperactivated ERK and reduces hyperproliferation of Nf1-deficient mast cells in vitro and in vivo. Genetic intercross of Nf1+/- × Rac2-/- mice; ERK activation assays; mast cell proliferation assays in vitro and in vivo; PI-3K inhibitor studies The Journal of experimental medicine High 11435472
2016 WASp deficiency in dendritic cells leads to increased Rac2 activation that maintains near-neutral phagosomal pH, supporting enhanced cross-presentation to CD8+ T cells; WASp and Rac2 signaling pathways are in balance in DCs. WASp-deficient DC conditional knockout mice; Rac2 activation assays; phagosomal pH measurement; cross-presentation assays; CD8+ T cell expansion Nature communications Medium 27425374
2005 Rac2 deficiency does not impair translocation of p47phox and p67phox to the plasma membrane; impaired NADPH oxidase activity in rac2-/- neutrophils can be rescued by exogenous arachidonic acid combined with PMA, suggesting Rac2 is required for optimal activity of the assembled oxidase complex through a mechanism that can be bypassed by arachidonic acid. Rac2 knockout neutrophils; p47phox and p67phox membrane translocation assays; superoxide production with exogenous AA; PKC inhibitor studies Journal of leukocyte biology Medium 16275890
2024 GDNF-secreted by Schwann cells phosphorylates MUC21 intracellular domain at S543 via CDK1 in PDAC cells; this phosphorylation facilitates interaction between MUC21 and RAC2, leading to membrane anchoring and activation of RAC2, which activates the JNK/ZEB1/EMT axis to promote pancreatic cancer perineural invasion and metastasis. Co-immunoprecipitation of MUC21 and RAC2; CDK1 phosphorylation assay; site-directed mutagenesis of S543; RAC2 activity assays; in vivo metastasis models Oncogene Medium 39020072
2024 Functionally characterized 23 RAC2 mutations: constitutively active RAS-like mutations cause neonatal SCID; dominant-negative mutations cause LAD-like disease; dominant-activating mutations cause CID. Downstream effector assays (superoxide production, PAK1 binding, AKT activation, protein stability) and confocal microscopy show altered actin assembly (membrane ruffling, macropinosomes) and abnormal protein localization for mutant RAC2 proteins. Heterologous expression of RAC2 mutants; superoxide production assays; PAK1-binding assays; AKT activation; protein stability assays; confocal microscopy of actin/membrane ruffling; clinical data from 54 patients Blood High 38194689
2023 Human-tissue-scale mechanical forces drive foreign-body response via RAC2 mechanotransduction signaling in a subpopulation of mechanoresponsive myeloid cells; pharmacological or genetic inhibition of RAC2 substantially reduces the pathological FBR. Vibrating silicone implant model in mice to apply human-tissue-scale forces; Rac2 genetic knockout; pharmacological Rac2 inhibition; cellular/molecular analysis of myeloid cell RAC2 activation Nature biomedical engineering Medium 37749310

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 443 10072071
2003 Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases. Science (New York, N.Y.) 398 14564009
2000 Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. Proceedings of the National Academy of Sciences of the United States of America 347 10758162
2004 Cdc42, Rac1, and Rac2 display distinct patterns of activation during phagocytosis. Molecular biology of the cell 301 15169870
2000 Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 270 10961859
2003 Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science (New York, N.Y.) 210 14564011
2004 Requirement of Rac1 and Rac2 expression by mature dendritic cells for T cell priming. Science (New York, N.Y.) 197 15326354
1994 Cytosolic guanine nucleotide-binding protein Rac2 operates in vivo as a component of the neutrophil respiratory burst oxidase. Transfer of Rac2 and the cytosolic oxidase components p47phox and p67phox to the submembranous actin cytoskeleton during oxidase activation. The Journal of biological chemistry 167 8120032
2001 Rac2 is an essential regulator of neutrophil nicotinamide adenine dinucleotide phosphate oxidase activation in response to specific signaling pathways. Journal of immunology (Baltimore, Md. : 1950) 158 11145705
2006 Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. Journal of cell science 156 16772332
2012 Rac2-MRC-cIII-generated ROS cause genomic instability in chronic myeloid leukemia stem cells and primitive progenitors. Blood 150 22411871
1999 Phosphoinositide 3-kinase-dependent and -independent activation of the small GTPase Rac2 in human neutrophils. The Journal of biological chemistry 150 10364257
2005 The arachidonic acid-binding protein S100A8/A9 promotes NADPH oxidase activation by interaction with p67phox and Rac-2. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 149 15642721
2011 NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut 148 21900546
2008 Regulation of the phagocyte NADPH oxidase activity: phosphorylation of gp91phox/NOX2 by protein kinase C enhances its diaphorase activity and binding to Rac2, p67phox, and p47phox. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 139 19028840
2000 Rac2 stimulates Akt activation affecting BAD/Bcl-XL expression while mediating survival and actin function in primary mast cells. Immunity 134 10843388
2000 Role of the guanosine triphosphatase Rac2 in T helper 1 cell differentiation. Science (New York, N.Y.) 134 10864872
2008 Activation of the small GTPase Rac2 via the B cell receptor regulates B cell adhesion and immunological-synapse formation. Immunity 127 18191593
1991 Carboxyl-terminal isoprenylation of ras-related GTP-binding proteins encoded by rac1, rac2, and ralA. The Journal of biological chemistry 127 1903399
2004 Rac2 is critical for neutrophil primary granule exocytosis. Blood 124 15073033
2011 Dual roles for Rac2 in neutrophil motility and active retention in zebrafish hematopoietic tissue. Developmental cell 120 22014524
2008 Identifying the relative contributions of Rac1 and Rac2 to osteoclastogenesis. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 117 17922611
2005 P-Rex1 is a primary Rac2 guanine nucleotide exchange factor in mouse neutrophils. Current biology : CB 110 16243036
2014 Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo. PloS one 109 24770346
1996 Mechanisms of NADPH oxidase activation: translocation of p40phox, Rac1 and Rac2 from the cytosol to the membranes in human neutrophils lacking p47phox or p67phox. The Biochemical journal 108 8670049
2004 Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. Journal of immunology (Baltimore, Md. : 1950) 107 15528331
2002 Chemoattractant-stimulated Rac activation in wild-type and Rac2-deficient murine neutrophils: preferential activation of Rac2 and Rac2 gene dosage effect on neutrophil functions. Journal of immunology (Baltimore, Md. : 1950) 107 12391220
2016 Rac2 Modulates Atherosclerotic Calcification by Regulating Macrophage Interleukin-1β Production. Arteriosclerosis, thrombosis, and vascular biology 103 27834690
2001 Hyperactivation of p21(ras) and the hematopoietic-specific Rho GTPase, Rac2, cooperate to alter the proliferation of neurofibromin-deficient mast cells in vivo and in vitro. The Journal of experimental medicine 101 11435472
2001 Deficiency of small GTPase Rac2 affects T cell activation. The Journal of experimental medicine 97 11581314
2007 Rac1 and Rac2 differentially regulate actin free barbed end formation downstream of the fMLP receptor. The Journal of cell biology 96 17954607
2002 The Rac2 guanosine triphosphatase regulates B lymphocyte antigen receptor responses and chemotaxis and is required for establishment of B-1a and marginal zone B lymphocytes. Journal of immunology (Baltimore, Md. : 1950) 95 11907095
2008 Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development. Blood 92 18579797
1995 Function of wild-type or mutant Rac2 and Rap1a GTPases in differentiated HL60 cell NADPH oxidase activation. Blood 90 7833480
2003 Human monocytes use Rac1, not Rac2, in the NADPH oxidase complex. The Journal of biological chemistry 84 12912997
2011 Pathogen-derived effectors trigger protective immunity via activation of the Rac2 enzyme and the IMD or Rip kinase signaling pathway. Immunity 82 22018470
2005 Drosophila melanogaster Rac2 is necessary for a proper cellular immune response. Genes to cells : devoted to molecular & cellular mechanisms 81 16098145
2002 Repression of rac2 mRNA expression by Anaplasma phagocytophila is essential to the inhibition of superoxide production and bacterial proliferation. Journal of immunology (Baltimore, Md. : 1950) 80 12471136
2001 Biochemical and biological characterization of a human Rac2 GTPase mutant associated with phagocytic immunodeficiency. The Journal of biological chemistry 79 11278678
2012 Zymosan induces NADPH oxidase activation in human neutrophils by inducing the phosphorylation of p47phox and the activation of Rac2: involvement of protein tyrosine kinases, PI3Kinase, PKC, ERK1/2 and p38MAPkinase. Biochemical pharmacology 66 23085266
2002 Rac2 regulation of phospholipase C-beta 2 activity and mode of membrane interactions in intact cells. The Journal of biological chemistry 65 12509427
2019 Dominant activating RAC2 mutation with lymphopenia, immunodeficiency, and cytoskeletal defects. Blood 61 30723080
2008 Parallel phosphatidylinositol 3-kinase (PI3K)-dependent and Src-dependent pathways lead to CXCL8-mediated Rac2 activation and chemotaxis. The Journal of biological chemistry 59 18662984
2013 Hematopoietic-specific Rho GTPases Rac2 and RhoH and human blood disorders. Experimental cell research 58 23850828
2013 Interaction of inducible nitric oxide synthase with rac2 regulates reactive oxygen and nitrogen species generation in the human neutrophil phagosomes: implication in microbial killing. Antioxidants & redox signaling 56 23875749
2003 Continuous translocation of Rac2 and the NADPH oxidase component p67(phox) during phagocytosis. The Journal of biological chemistry 56 14623873
2010 Rac1 and Rac2 GTPases are necessary for early erythropoietic expansion in the bone marrow but not in the spleen. Haematologica 51 20065081
2014 Chemokine-coupled β2 integrin-induced macrophage Rac2-Myosin IIA interaction regulates VEGF-A mRNA stability and arteriogenesis. The Journal of experimental medicine 49 25180062
2010 Rac2 GTPase deficiency depletes BCR-ABL+ leukemic stem cells and progenitors in vivo. Blood 49 20407032
2005 Rac2 regulates neutrophil chemotaxis, superoxide production, and myeloid colony formation through multiple distinct effector pathways. Journal of immunology (Baltimore, Md. : 1950) 49 15814684
2002 Rac2-deficient mice display perturbed T-cell distribution and chemotaxis, but only minor abnormalities in T(H)1 responses. Immunology and cell biology 49 12067410
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
2011 RAC2, AEP, and ICAM1 expression are associated with CNS disease in a mouse model of pre-B childhood acute lymphoblastic leukemia. Blood 45 21606482
2010 RtxA1-induced expression of the small GTPase Rac2 plays a key role in the pathogenicity of Vibrio vulnificus. The Journal of infectious diseases 45 19919301
2016 The Phospholipase Cγ2 Mutants R665W and L845F Identified in Ibrutinib-resistant Chronic Lymphocytic Leukemia Patients Are Hypersensitive to the Rho GTPase Rac2 Protein. The Journal of biological chemistry 44 27542411
2016 Rac2 Functions in Both Neutrophils and Macrophages To Mediate Motility and Host Defense in Larval Zebrafish. Journal of immunology (Baltimore, Md. : 1950) 44 27837107
2005 Rac2-deficient hematopoietic stem cells show defective interaction with the hematopoietic microenvironment and long-term engraftment failure. Stem cells (Dayton, Ohio) 44 15749928
2011 Phospholipase D2 (PLD2) is a guanine nucleotide exchange factor (GEF) for the GTPase Rac2. Proceedings of the National Academy of Sciences of the United States of America 42 22106281
2005 Impaired NADPH oxidase activity in Rac2-deficient murine neutrophils does not result from defective translocation of p47phox and p67phox and can be rescued by exogenous arachidonic acid. Journal of leukocyte biology 40 16275890
2003 Rac2 specificity in macrophage integrin signaling: potential role for Syk kinase. The Journal of biological chemistry 40 12917394
2020 RAC2 and primary human immune deficiencies. Journal of leukocyte biology 39 32542921
2011 The mechanism of cell membrane ruffling relies on a phospholipase D2 (PLD2), Grb2 and Rac2 association. Cellular signalling 39 21419846
2022 Macrophage ALDH2 (Aldehyde Dehydrogenase 2) Stabilizing Rac2 Is Required for Efferocytosis Internalization and Reduction of Atherosclerosis Development. Arteriosclerosis, thrombosis, and vascular biology 38 35354308
1994 Synthesis of androst-5-en-7-ones and androsta-3,5-dien-7-ones and their related 7-deoxy analogs as conformational and catalytic probes for the active site of aromatase. Journal of medicinal chemistry 37 8035427
2010 Sbds is required for Rac2-mediated monocyte migration and signaling downstream of RANK during osteoclastogenesis. Blood 35 21084708
2002 The TRQQKRP motif located near the C-terminus of Rac2 is essential for Rac2 biologic functions and intracellular localization. Blood 34 12176888
2017 Rac2 deficiency attenuates CCl4-induced liver injury through suppressing inflammation and oxidative stress. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 32 28759751
2005 CXCL9 inhibits eosinophil responses by a CCR3- and Rac2-dependent mechanism. Blood 32 15802529
2020 The Impression of a Nonexisting Catalytic Effect: The Role of CotB2 in Guiding the Complex Biosynthesis of Cyclooctat-9-en-7-ol. Journal of the American Chemical Society 31 33289561
2014 Rac2 is involved in bleomycin-induced lung inflammation leading to pulmonary fibrosis. Respiratory research 31 24970330
2011 The exquisite regulation of PLD2 by a wealth of interacting proteins: S6K, Grb2, Sos, WASp and Rac2 (and a surprise discovery: PLD2 is a GEF). Cellular signalling 31 21740967
2016 Deletion of Wiskott-Aldrich syndrome protein triggers Rac2 activity and increased cross-presentation by dendritic cells. Nature communications 30 27425374
2007 Rac2 is a major actor of Drosophila resistance to Pseudomonas aeruginosa acting in phagocytic cells. Genes to cells : devoted to molecular & cellular mechanisms 30 17903178
2023 Allometrically scaling tissue forces drive pathological foreign-body responses to implants via Rac2-activated myeloid cells. Nature biomedical engineering 29 37749310
2007 Genetic and pharmacologic evidence implicating the p85 alpha, but not p85 beta, regulatory subunit of PI3K and Rac2 GTPase in regulating oncogenic KIT-induced transformation in acute myeloid leukemia and systemic mastocytosis. Blood 29 17483298
2019 Heterozygous activating mutation in RAC2 causes infantile-onset combined immunodeficiency with susceptibility to viral infections. Clinical immunology (Orlando, Fla.) 28 31071452
2009 Regulation of inflammation by Rac2 in immune complex-mediated acute lung injury. American journal of physiology. Lung cellular and molecular physiology 28 19801448
1997 Guanine nucleotide binding properties of Rac2 mutant proteins and analysis of the responsiveness to guanine nucleotide dissociation stimulator. Biochemistry 28 9012677
2017 Rac2 is required for alternative macrophage activation and bleomycin induced pulmonary fibrosis; a macrophage autonomous phenotype. PloS one 27 28817691
2009 Suppressed hindlimb perfusion in Rac2-/- and Nox2-/- mice does not result from impaired collateral growth. American journal of physiology. Heart and circulatory physiology 27 19151256
2020 Additive effects of simulated microgravity and ionizing radiation in cell death, induction of ROS and expression of RAC2 in human bronchial epithelial cells. NPJ microgravity 26 33298974
2019 Nonconserved miR-608 suppresses prostate cancer progression through RAC2/PAK4/LIMK1 and BCL2L1/caspase-3 pathways by targeting the 3'-UTRs of RAC2/BCL2L1 and the coding region of PAK4. Cancer medicine 26 31389670
2017 (22β,25R)-3β-Hydroxy-spirost-5-en-7-iminoxy-heptanoic acid exhibits anti-prostate cancer activity through caspase pathway. Steroids 26 28143704
2009 Differential regulation of phospholipase C-beta2 activity and membrane interaction by Galphaq, Gbeta1gamma2, and Rac2. The Journal of biological chemistry 26 20007712
2006 Cytokine expression and AIF-1-mediated activation of Rac2 in vascular smooth muscle cells: a role for Rac2 in VSMC activation. American journal of physiology. Cell physiology 26 16987989
2002 Activation of Rac-1, Rac-2, and Cdc42 by hemopoietic growth factors or cross-linking of the B-lymphocyte receptor for antigen. Blood 26 12384416
2000 Differential expression and regulation of GTPases (RhoA and Rac2) and GDIs (LyGDI and RhoGDI) in neutrophils from patients with severe congenital neutropenia. Blood 26 10779444
2017 Overexpression of microRNA-722 fine-tunes neutrophilic inflammation by inhibiting Rac2 in zebrafish. Disease models & mechanisms 25 28954734
2016 RAC2-P38 MAPK-dependent NADPH oxidase activity is associated with the resistance of quiescent cells to ionizing radiation. Cell cycle (Georgetown, Tex.) 25 27936335
2003 Activation of Rac2 and Cdc42 on Fc and complement receptor ligation in human neutrophils. Journal of leukocyte biology 25 12960248
2002 DOCK2 mediates T cell receptor-induced activation of Rac2 and IL-2 transcription. Biochemical and biophysical research communications 25 12176041
2024 GDNF-induced phosphorylation of MUC21 promotes pancreatic cancer perineural invasion and metastasis by activating RAC2 GTPase. Oncogene 24 39020072
2011 Evidence for two CRIB domains in phospholipase D2 (PLD2) that the enzyme uses to specifically bind to the small GTPase Rac2. The Journal of biological chemistry 24 21378159
2005 Neutrophil primary granule release and maximal superoxide generation depend on Rac2 in a common signalling pathway. Canadian journal of physiology and pharmacology 24 15759052
2024 Clinical and functional spectrum of RAC2-related immunodeficiency. Blood 23 38194689
2011 Agonist activation of f-actin-mediated eosinophil shape change and mediator release is dependent on Rac2. International archives of allergy and immunology 23 21576984
1999 Expression and translocation of Rac2 in eosinophils during superoxide generation. Immunology 23 10540223
2018 RAC2 promotes abnormal proliferation of quiescent cells by enhanced JUNB expression via the MAL-SRF pathway. Cell cycle (Georgetown, Tex.) 22 29895215
2011 The role of SDF-1α/Rac pathway in the regulation of endothelial progenitor cell polarity; homing and expression of Rac1, Rac2 during endothelial repair. Molecular and cellular biochemistry 22 21964561
2002 RAC2 GTPase deficiency and myeloid cell dysfunction in human and mouse. Journal of pediatric hematology/oncology 22 12468931

Missed literature

Know a paper Affinage missed for RAC2? Flag it for the maintainers and the community.

No submissions yet.