Affinage

PLCG1

1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1 · UniProt P19174

Length
1290 aa
Mass
148.5 kDa
Annotated
2026-06-10
100 papers in source corpus 52 papers cited in narrative 52 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 5/5 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

PLCγ1 is a receptor- and integrin-coupled phospholipase that hydrolyzes PtdIns(4,5)P2 to generate the second messengers IP3 and DAG, transducing tyrosine-kinase signals into Ca²⁺ mobilization and downstream transcriptional programs across immune, vascular, neuronal, and developmental contexts (PMID:11094067, PMID:15944397, PMID:11796522). In T cells, PLCγ1 is recruited through its N-terminal SH2 domain to the phosphorylated adaptor LAT, an interaction that is necessary but insufficient for stable engagement and requires additional contributions from its SH3 and C-terminal SH2 domains together with SLP-76, Vav1, and c-Cbl (PMID:9846483, PMID:11390650, PMID:16467851); PLCγ1 itself cross-links LAT into phase-separated condensates and protects LAT from CD45-mediated dephosphorylation, reinforcing the signalosome (PMID:33929486). Activation proceeds by a stepwise mechanism in which SLP-76 pY173 binds the autoinhibited SH2(C) domain, displacing it to expose the docking surface for Itk, which then phosphorylates the critical activating residue Y783 via a noncanonical SH2–kinase interaction (PMID:19955438, PMID:25916191); productive enzyme activity drives Ca²⁺/NFAT and AP-1/NF-κB responses (PMID:11094067, PMID:31376383). Beyond lymphocytes, PLCγ1 transduces VEGFR2 signaling through pY1175 for endothelial specification and is negatively regulated by c-Cbl-dependent ubiquitination that suppresses its tyrosine phosphorylation without degradation (PMID:17372230, PMID:21242968, PMID:19706681); it acts cell-autonomously in endothelium for vasculogenesis and artery development and is required for erythropoiesis, cardiac contractility, and netrin-1/DCC-dependent axon guidance in vivo (PMID:11744703, PMID:15998812, PMID:19269286, PMID:30224412, PMID:25394487). Gain-of-function mutations in the autoinhibitory SH2 domain or catalytic region (e.g., R707Q, S345F, S1021F) confer constitutive, Y783-phosphorylation-independent enzyme activity that elevates IP3 and drives NFAT/NF-κB/AP-1 signaling, underlying angiosarcoma, cutaneous T-cell lymphoma, Sézary syndrome, and germline immune dysregulation (PMID:25252913, PMID:24497536, PMID:31376383, PMID:37422272).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1998 High

    Established the adaptor LAT as the upstream organizer required for TCR-driven PLCγ1 activation, defining where in the pathway PLCγ1 acts.

    Evidence Genetic complementation in LAT-deficient Jurkat cells with multiple signaling readouts

    PMID:9846483

    Open questions at the time
    • Did not define which PLCγ1 domains contact LAT
    • Mechanism of PLCγ1 catalytic activation not addressed
  2. 2001 High

    Assigned distinct functions to individual PLCγ1 domains, showing SH2(N) mediates LAT association and phosphorylation while SH3 binds SLP-76 and SH2(C) carries a separable signaling role.

    Evidence Domain-deletion mutagenesis, reciprocal co-IP, and reporter assays in Jurkat cells; PLCγ1-deficient Jurkat reconstitution

    PMID:11094067 PMID:11390650

    Open questions at the time
    • Structural basis of the noncanonical SH2(C) function unresolved
    • How Y783 phosphorylation links to enzyme activation not defined
  3. 2001 High

    Demonstrated PLCγ1 is essential and nonredundant in vivo for erythropoiesis and vasculogenesis, extending its role beyond immune signaling.

    Evidence Plcg1 knockout mouse embryo analysis with colony-forming and immunostaining assays

    PMID:11744703

    Open questions at the time
    • Upstream receptors driving these developmental roles not identified here
    • Downstream effectors unknown
  4. 2003 High

    Showed PLCγ1 participates in feedback signaling loops with kinases (c-Abl) and that its lipid-hydrolysis product depletion modulates partner kinase activity.

    Evidence Co-IP, kinase assays, PtdIns(4,5)P2 depletion, and chemotaxis assays

    PMID:12652307

    Open questions at the time
    • Physiological context of the c-Abl feedback loop limited
    • Reciprocal regulation in vivo untested
  5. 2005 High

    Defined PLCγ1 as a transducer of integrin and VEGF/FLT-1 signaling, linking Src-dependent Y783 phosphorylation to cell motility and cardiac contractility.

    Evidence Genetic KO/siRNA, Y783 mutagenesis, Src-family KO cells, zebrafish dead beat mutant cloning and rescue, and rat cardiomyocyte Ca²⁺ measurements

    PMID:15657076 PMID:15944397 PMID:15998812

    Open questions at the time
    • How integrin- versus RTK-driven activation differ mechanistically not fully resolved
    • Site specificity of phosphorylation under integrin engagement only partly mapped
  6. 2007 High

    Identified c-Cbl as a negative regulator that ubiquitinates PLCγ1 within a VEGFR-2 ternary complex to suppress its phosphorylation without degradation, controlling angiogenesis.

    Evidence Binding assays, VEGFR-2 mutagenesis, c-Cbl siRNA, ubiquitylation and angiogenesis assays; later confirmed in c-Cbl knockout mice

    PMID:17372230 PMID:21242968

    Open questions at the time
    • Structural basis of proteolysis-independent inhibition by ubiquitin unclear
    • Whether this regulation operates outside endothelium untested
  7. 2009 High

    Resolved the molecular activation switch in T cells: Itk docks via a noncanonical PLCγ1 SH2 surface to phosphorylate Y783, while PLCγ1 actively drives LAT phase separation and protects LAT phosphorylation.

    Evidence NMR spectroscopy, mutagenesis, in vitro phase-separation reconstitution, and dephosphorylation-protection assays

    PMID:19955438 PMID:33929486

    Open questions at the time
    • How condensate formation and Itk docking are temporally coordinated not fully defined
    • In vivo relevance of phase separation untested
  8. 2009 High

    Showed PLCγ1 acts cell-autonomously in endothelium downstream of VEGFR2 (via pY1175) for artery development and endothelial specification, requiring catalytic activity.

    Evidence Zebrafish allelic series with catalytic mutants and mosaic analysis; chimeric VEGFR2/VEGFR3 ES cell differentiation

    PMID:19269286 PMID:19706681

    Open questions at the time
    • Receptor-specific basis for VEGFR2 versus VEGFR3 selectivity at the PLCγ1 level only partly explained
    • Effector pathways downstream of catalytic activity in arteries not enumerated
  9. 2015 High

    Defined the priming step of activation: SLP-76 pY173 binds the autoinhibited SH2(C) domain, displacing it to expose the Itk recognition element and release Y783 for phosphorylation.

    Evidence NMR spectroscopy, quantitative binding, and competition assays with phosphopeptides

    PMID:25916191

    Open questions at the time
    • Full conformational cycle of the lipase in cells not visualized
    • Quantitative ordering relative to LAT recruitment unresolved
  10. 2018 High

    Extended PLCγ1 function to neuronal axon guidance in vivo and to CD95-driven Ca²⁺ signaling in inflammation, establishing therapeutically targetable interactions.

    Evidence Neuronal progenitor-specific Plcg1 knockout with brain structural phenotypes; CD95 CID inhibitor screen, co-IP, Ca²⁺ flux, and lupus mouse model

    PMID:30224412 PMID:30429604

    Open questions at the time
    • Downstream cytoskeletal effectors of netrin-1/DCC-PLCγ1 only partly defined
    • Generalizability of CID-targeting beyond modeled disease untested
  11. 2014 Medium

    Established that recurrent autoinhibitory-domain and catalytic mutations confer constitutive, Y783-independent PLCγ1 activity driving lymphoma and angiosarcoma.

    Evidence Targeted sequencing plus reconstitution of R707Q and S345F mutants with IP3, Ca²⁺, NFAT reporter, and invasion readouts

    PMID:24497536 PMID:25252913

    Open questions at the time
    • Structural mechanism by which SH2-domain mutations relieve autoinhibition only inferred
    • In vivo tumorigenicity of single mutants in autochthonous models not shown
  12. 2019 High

    Generalized the gain-of-function model by showing diverse Sézary-syndrome mutations raise inositol phosphate output and NF-κB/AP-1/NFAT activation independent of Y783 phosphorylation.

    Evidence In vitro inositol phosphate assays, multiple reporter assays, and Y783-deficient mutant analysis across nine mutations

    PMID:31376383

    Open questions at the time
    • Per-mutation structural consequences not individually resolved
    • Therapeutic vulnerability of mutant-driven signaling not tested here
  13. 2023 High

    Demonstrated that a de novo germline gain-of-function variant causes a Mendelian immune-dysregulation disorder via elevated IP3/Ca²⁺ and inflammatory transcription, reversible by PLCγ1 or JAK inhibition.

    Evidence Whole exome sequencing, IP3 ELISA, Ca²⁺ flux, scRNA-seq, and inhibitor reversal in patient cells

    PMID:37422272

    Open questions at the time
    • Genotype-phenotype spectrum of germline PLCG1 variants incomplete
    • Long-term consequences in human carriers beyond initial characterization unknown
  14. 2024 Medium

    Identified PLCγ1 as a chaperone-mediated autophagy substrate, linking its turnover to Ca²⁺ homeostasis and cellular senescence.

    Evidence Proteomic substrate identification, immunoprecipitation, Ca²⁺ assays, and LAMP2A/Plcg1 manipulation in a rat disc-degeneration model

    PMID:39212196

    Open questions at the time
    • CMA targeting motif on PLCγ1 not mapped
    • Single-lab finding awaiting independent confirmation

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct upstream contexts (RTK, integrin, immune receptor, mechanosensation) select among PLCγ1's varied effector outputs and how oncogenic versus germline activating mutations differentially rewire signaling remain incompletely defined.
  • No unified structural model linking each activation route to a specific output
  • Context-dependent partner usage not systematically compared

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016787 hydrolase activity 4 GO:0008289 lipid binding 3 GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0140096 catalytic activity, acting on a protein 3
Localization
GO:0005886 plasma membrane 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 2
Pathway
R-HSA-1643685 Disease 5 R-HSA-168256 Immune System 5 R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-5357801 Programmed Cell Death 2
Partners
CBLFGFR2ITKLATRAC1SLP-76SRCVEGFR2
Complex memberships
LAT signalosomeVEGFR2/PLCγ1/c-Cbl ternary complex

Evidence

Reading pass · 52 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1998 LAT (pp36) is required for TCR-mediated activation of PLCγ1: T cells deficient in LAT fail to show increases in intracellular calcium, Ras activation, and IL-2 gene expression, and reexpression of LAT restores PLCγ1 signaling, placing LAT upstream of PLCγ1 in the TCR pathway. Functional reconstitution in LAT-deficient Jurkat (J.CaM2) mutant cell line with LAT re-expression; epistasis analysis Immunity High 9846483
2001 SLP-76 directly interacts with the SH3 domain of PLCγ1 via a 67-amino-acid proline-rich 'P-1 domain'; this constitutive interaction is required for TCR-mediated activation of Erk, PLCγ1, and NFAT. The SH2(N) domain of PLCγ1 is required for association with LAT and for PLCγ1 tyrosine phosphorylation, whereas the SH2(C) domain mediates a non-Ca²⁺ signaling function linked to IL-2 promoter activation. Structure-function deletion mutagenesis of SLP-76 and PLCγ1; co-immunoprecipitation; reconstitution in Jurkat cells; NFAT and IL-2 reporter assays Molecular and cellular biology High 11390650
2000 PLCγ1 is required for TCR-dependent Ca²⁺ mobilization and NFAT activation; the SH2(C) domain is necessary for RE/AP and IL-2 promoter activation after TCR+CD28 costimulation; the major phosphorylation site Tyr783 is required for these transcriptional responses. The SH2(N) domain is required for LAT association and PLCγ1 tyrosine phosphorylation but not for IL-2 promoter activation. Isolation and characterization of PLC-γ1-deficient Jurkat sublines (J.γ1 and P98); reconstitution with wild-type and domain-mutant PLCγ1 constructs; Ca²⁺ flux, NFAT, and IL-2 reporter assays Molecular and cellular biology High 11094067
2001 Plcg1 nullizygous mouse embryos lack erythroid progenitors (BFU, CFU, Ter119+) and show severely diminished vasculogenesis (reduced PECAM-1 and Flk-1 expression), demonstrating that PLCγ1 is required for erythropoiesis and vasculogenesis in vivo; PLCγ2 cannot substitute. Plcg1 knockout mouse analysis; colony-forming unit assays; immunostaining for Ter119, PECAM-1, Flk-1 The Journal of biological chemistry High 11744703
2006 The N-terminal SH2 domain of PLCγ1 is necessary but not sufficient for recruitment to the LAT signaling complex; either the SH3 or C-terminal SH2 domain, together with Vav1, c-Cbl, and SLP-76, are required to stabilize PLCγ1 recruitment. All three SH domains are required for phosphorylation of PLCγ1 Y783, which is critical for enzyme activation. Biochemical co-immunoprecipitation combined with real-time fluorescent imaging; domain-deletion mutant analysis in T cells The EMBO journal High 16467851
2005 PLCγ1 is required for cardiac contractility in the embryonic zebrafish heart; the dead beat mutation maps to plcg1. VEGF signals through FLT-1 receptor to activate PLCγ1, increasing Ca²⁺ transients and exerting a positive inotropic effect in cardiomyocytes; this pathway functions in rat ventricular cardiomyocytes as well. Forward genetic cloning of zebrafish dead beat mutant; cardiac-specific PLCγ1 rescue; VEGF pathway epistasis; Ca²⁺ transient measurements in rat cardiomyocytes Genes & development High 15998812
2009 Vegf/Plcg1 signaling acts at multiple time points downstream of receptor tyrosine kinases to mediate distinct aspects of artery development in zebrafish; in vivo structure-function analysis demonstrates a requirement for Plcg1 catalytic activity; mosaic analysis establishes that plcg1 functions cell-autonomously in endothelial cells. Forward genetic screen in zebrafish; allelic series of plcg1 mutations; in vivo structure-function analysis; mosaic analysis Developmental biology High 19269286
2003 Functional PLCγ1 is required for c-Abl activation by PDGFR: PLC-γ1-mediated hydrolysis of PtdIns(4,5)P2 (decreasing its levels) increases Abl kinase activity; c-Abl functions downstream of PLCγ1 in chemotaxis; PLCγ1 and c-Abl form a complex in cells enhanced by PDGF stimulation; activated c-Abl phosphorylates PLCγ1 and negatively modulates its function, constituting a feedback loop. Co-immunoprecipitation; kinase assays; inositol phosphatase (Inp54) overexpression to deplete PtdIns(4,5)P2; kinase-inactive c-Abl dominant negative rescue; chemotaxis assay Nature cell biology High 12652307
2005 PLCγ1 is essential for integrin-mediated cell motility: depletion by siRNA, pharmacological inhibition, or genetic knockout prevents cell protrusions, spreading, and elongation after integrin engagement; Tyr783 phosphorylation (by Src kinase acting downstream of β1 integrin) and SH2 domains are required; PLCγ1 co-immunoprecipitates with Src after fibronectin-induced integrin activation in a FAK-independent manner. siRNA knockdown; PLCγ1−/− cells; site-directed mutagenesis at Y783; Src kinase inhibitor; co-immunoprecipitation; morphology/invasion assays Journal of cell science High 15944397
2005 Fibronectin selectively increases PLCγ1 phosphorylation at Tyr783 (but not Tyr771 or Tyr1253) via Src kinase (not EGFR kinase) downstream of β1 integrin; mutagenesis of Tyr783 abrogates fibronectin-dependent cell adhesion; PLCγ1 co-immunoprecipitates with Src after fibronectin stimulation, and this is FAK-independent. Plcg1−/− vs. re-expressed fibroblasts; site-directed mutagenesis; Src-family kinase KO cells; FAK KO cells; co-immunoprecipitation; adhesion assays Journal of cell science High 15657076
2007 c-Cbl E3 ubiquitin ligase constitutively associates with PLCγ1 via its C-terminal domain and conditionally interacts with VEGFR-2; full c-Cbl activation requires direct association with VEGFR-2 phosphotyrosines Y1052/Y1057 and indirect association with pY1173 via PLCγ1. The VEGFR-2/PLCγ1/c-Cbl ternary complex promotes ubiquitylation of PLCγ1 and suppresses its tyrosine phosphorylation by a proteolysis-independent mechanism, negatively regulating angiogenesis. In vitro and in vivo binding assays; site-directed mutagenesis of VEGFR-2; siRNA silencing of c-Cbl; ubiquitylation assays; angiogenesis assays Proceedings of the National Academy of Sciences of the United States of America High 17372230
2011 c-Cbl-dependent ubiquitination of PLCγ1 selectively inhibits its tyrosine phosphorylation (without inducing degradation), suppressing VEGF-driven Ca²⁺ release, endothelial proliferation, and angiogenesis in vivo; genetic inactivation of c-Cbl in mice results in enhanced tumor angiogenesis and retinal neovascularization. c-Cbl knockout mice; endothelial cell proliferation and tube formation assays; Ca²⁺ release measurement; ubiquitination assay Oncogene High 21242968
1998 FcεRI cross-linking activates PLCγ1 in mast cells; PLCγ1 is cytosolic at rest and translocates to plasma membrane ruffles upon antigen stimulation; this translocation and activation (but not that of PLCγ2) is blocked by the PI3-kinase inhibitor wortmannin, implicating PI3-kinase in PLCγ1 phosphorylation, translocation, and activation. Immune complex phospholipase assays; subcellular fractionation; immunofluorescence; wortmannin inhibition Molecular biology of the cell Medium 9450969
2001 EGF induces rapid translocation of PLCγ1-GFP from cytoplasm to plasma membrane (actin-dependent, PI3K-independent), and at later times to endosomes co-localizing with internalized EGFR; EGF-induced PLCγ1 concentrates in caveolae, and disruption of caveolae ablates EGF-induced Ca²⁺ mobilization. Live-cell GFP imaging; subcellular fractionation; methyl-β-cyclodextrin caveolae disruption; Ca²⁺ mobilization assay Experimental cell research Medium 11412035
2004 PKCθ promotes a positive feedback loop in T cell restimulation by enhancing TCR/CD28-induced PLCγ1 tyrosine phosphorylation and activation; this requires the Tec kinase Tec (not Itk or Rlk) acting downstream of PKCθ through a pleckstrin-homology domain-dependent association of Tec with PKCθ, linking the PKCθ pathway to Ca²⁺ signaling and AP-1 activation. PKCθ−/− primary T cells; dominant-negative PLCγ1 and Tec mutants; AP-1/NFAT reporter assays; Ca²⁺ mobilization; co-immunoprecipitation European journal of immunology Medium 15214048
2009 PLCγ1 SH3 domain directly interacts with Rac1 via the Rac1 (106)PNTP(109) motif; this interaction is required for EGF-induced Rac1 activation in vivo; purified PLCγ1 SH3 domain acts as a Rac1 guanine nucleotide exchange factor in vitro, mediating EGF-induced F-actin formation and cell migration. Co-immunoprecipitation; direct binding; in vitro GEF assay with purified proteins; mutagenesis; siRNA knockdown; F-actin and migration assays Molecular endocrinology Medium 19264842
2009 PLCγ1 directly cross-links LAT through its two SH2 domains, promoting phase separation of LAT into liquid-like condensates; PLCγ1 protects LAT from dephosphorylation by the phosphatase CD45 and promotes LAT-dependent ERK activation and SLP76 phosphorylation; PLCγ1 concentration has a nonmonotonic effect on LAT cluster size. Reconstitution of phase separation in vitro; mutagenesis; biochemical dephosphorylation protection assays; ERK and SLP76 phosphorylation assays; computer simulations The Journal of cell biology High 33929486
2009 Itk phosphorylates PLCγ1 at Y783 through a direct, phosphotyrosine-independent interaction between the SH2 domain of PLCγ1 and the kinase domain of Itk; NMR spectroscopy and mutagenesis define this nonclassical SH2 binding surface; disruption of this docking interaction attenuates T cell signaling. NMR spectroscopy; mutagenesis; in vitro binding and phosphorylation assays; T cell signaling readouts Proceedings of the National Academy of Sciences of the United States of America High 19955438
2012 F-actin polymerization drives actin retrograde flow at the immunological synapse; disruption of retrograde flow arrests microcluster centralization and inhibits PLCγ1 phosphorylation within microclusters (leaving Zap70 activity intact), thereby suppressing sustained Ca²⁺ signaling at the ER store level. Pharmacological inhibitors of F-actin dynamics; live-cell imaging of microcluster movement; PLCγ1 phosphorylation by immunofluorescence; Ca²⁺ signaling measurements The Journal of cell biology Medium 22665519
2012 PLCγ1 activation is critical for myogenic constriction of cerebral arteries: pressure (via Src tyrosine kinase) activates PLCγ1, which generates IP3; IP3 sensitizes IP3 receptors to Ca²⁺ influx through mechanosensitive TRPC6, synergistically increasing IP3R-mediated Ca²⁺ release to activate TRPM4 currents and smooth muscle depolarization; proximity ligation assays demonstrate colocalization of PLCγ1, TRPC6, and TRPM4. Pharmacological inhibitors; Ca²⁺ imaging in isolated cerebral arteries; proximity ligation assay; Src inhibitor; IP3 measurement Science signaling Medium 24866019
2014 The recurrent PLCG1 R707Q mutation in angiosarcomas affects the autoinhibitory SH2 domain and causes constitutive activation: ectopic expression in endothelial cells shows reduced PLCγ1-Y783 phosphorylation yet increased IP3, Ca²⁺-dependent calcineurin activation, c-RAF/MEK/ERK1/2 phosphorylation, and cofilin activation compared with wild-type; R707Q increases apoptosis resistance and cell migration/invasion without affecting proliferation. Targeted next-generation sequencing; ectopic expression of wild-type vs. R707Q in endothelial cells; IP3 measurement; Ca²⁺ signaling; phospho-western blotting; migration and invasion assays Cancer research Medium 25252913
2014 PLCG1 S345F (and other gain-of-function mutations) in cutaneous T-cell lymphoma increase downstream signaling toward NFAT activation; immunohistochemistry showed strong NFAT nuclear staining in PLCG1-mutated CTCL cases; functional studies demonstrated that PLCG1 mutants elicit increased NFAT activation, and inhibition reduced CTCL cell proliferation and viability. Targeted sequencing; NFAT immunohistochemistry; functional overexpression of PLCG1 mutants; NFAT reporter assays; inhibitor treatment with proliferation/viability readout Blood Medium 24497536
2019 Nine PLCG1 mutations identified in Sézary syndrome confer gain-of-function PLCγ1 activity through increased inositol phosphate production and downstream NFκB, AP-1, and NFAT transcriptional activation; these activating mutations do not require Y783 phosphorylation for downstream signaling, in contrast to wild-type PLCγ1. In vitro inositol phosphate assays; NFκB/AP-1/NFAT luciferase reporter assays; Y783 phosphorylation-deficient mutant analysis; expression in cell lines The Journal of investigative dermatology High 31376383
2009 VEGFR2 Y1175 signaling through PLCγ1 is required for endothelial specification of VEGFR2+ vascular progenitors from embryonic stem cells; VEGFR3 does not activate PLCγ1 and does not direct endothelial differentiation, distinguishing the VEGFR2-PLCγ1 axis as unique for endothelial specification. Chimeric VEGFR2/VEGFR3 receptors in ES cell differentiation system; PLCγ1 activation assays; endothelial differentiation markers Journal of cell science Medium 19706681
2012 PDK1 regulates PLCγ1 activation through direct association of the two enzymes and modulation of PLCγ1 tyrosine phosphorylation; this PDK1-PLCγ1 pathway is important for cancer cell invasion. Co-immunoprecipitation; PLCγ1 tyrosine phosphorylation assays; cancer cell invasion assays; PDK1 inhibition/knockdown Journal of cell science Medium 22454520
2014 In unstimulated cells, the SH3 domain of PLCγ1 (not its SH2 domains) competes with the C-terminal SH3 domain of Grb2 for a phosphorylation-independent binding site at the very C-terminus of FGFR2; reduction of Grb2 allows PLCγ1 to bind FGFR2 basally, upregulating phospholipase activity and increasing PtdIns(4,5)P2 turnover, Ca²⁺, and cell invasion. Structural and binding analysis; competition assays; PtdIns(4,5)P2 turnover; Ca²⁺ measurements; invasion assays in cells with reduced Grb2 Nature structural & molecular biology High 24440983
2003 Tr-kit promotes formation of a multimolecular complex containing Fyn, PLCγ1, and Sam68; tr-kit promotes association of Sam68 with PLCγ1 and Fyn via the PLCγ1 SH3 domain; this leads to PLCγ1 phosphorylation by Fyn and alters Sam68 subcellular localization and its release from bound RNA. Co-immunoprecipitation with antibodies to each complex partner; SH3 domain binding; in-cell expression studies; RNA binding assays Oncogene Medium 14647465
2011 LKB1 is directly phosphorylated by Lck at tyrosines 36, 261, and 365; LKB1 interacts predominantly with LAT and PLCγ1 following TCR stimulation; loss of LKB1 impairs recruitment of PLCγ1 to the LAT signalosome and reduces PLCγ1 tyrosine phosphorylation, causing defective thymocyte positive selection. Lck-Cre/CD4-Cre conditional LKB1 knockout mice; co-immunoprecipitation; tyrosine phosphorylation analysis; T cell signaling and thymocyte development assays The EMBO journal Medium 21487392
2015 Scaffold protein SLP-76 pY173IDR motif binds to the C-terminal SH2 domain (SH2C) of PLCγ1 with significant affinity despite not conforming to the canonical pY-SH2 recognition motif; this interaction competes with the autoinhibited conformation of the SH2C domain, exposing the ITK recognition element and releasing Y783 for ITK-mediated phosphorylation and PLCγ1 activation. NMR spectroscopy; mutagenesis; in vitro binding assays; competition assays with phosphopeptides Journal of molecular biology High 25916191
2012 RIAM (Rap1-GTP-interacting adaptor molecule) regulates TCR-mediated signaling by controlling translocation of phosphorylated PLCγ1 to the actin cytoskeleton, which is required to bring PLCγ1 close to its substrate PtdIns(4,5)P2; loss of RIAM impairs IP3 generation, Ca²⁺ mobilization, NFAT nuclear translocation, and IL-2 expression. shRNA knockdown of RIAM; IP3 assay; Ca²⁺ mobilization; NFAT localization; co-localization of pPLCγ1 with actin; reconstitution with RIAM Science signaling Medium 19952372
2018 PLCγ1 mediates axonal guidance downstream of the netrin-1/DCC complex through Src kinase activation; netrin-1/DCC activates PLCγ1 to induce actin cytoskeleton rearrangement; neuronal progenitor-specific knockout of Plcg1 in mice causes axon guidance defects in the mesencephalon and adult structural alterations in the corpus callosum, substantia innominata, and olfactory tubercle. Conditional neuronal progenitor-specific Plcg1 knockout mice; PLCγ1 activation assays; actin rearrangement assays; brain structural analysis in adults EMBO reports High 30224412
2018 CD95 (soluble CD95L/s-CD95L) recruits PLCγ1 to the calcium-inducing domain (CID) within CD95, triggering Ca²⁺ signaling and Th17 inflammatory cell accumulation; the HIV protease inhibitor ritonavir disrupts the CD95-PLCγ1 interaction; CID peptidomimetics designed to block this interaction abrogate CD95-driven Ca²⁺ response and Th17 transmigration, and reduce lupus symptoms in mice. Large-scale inhibitor screen; structure-activity relationship; co-immunoprecipitation; Ca²⁺ flux assay; Th17 transmigration assay; in vivo lupus mouse model Nature chemical biology High 30429604
2012 PLCγ1 signaling (specifically hypoxia-induced ROS-dependent PLCγ1 activation via mitochondrial complex III) generates IP3, triggers IP3R-mediated Ca²⁺ release, and mediates hypoxic vasoconstriction in pulmonary arterial smooth muscle cells; this pathway is specific to pulmonary (not mesenteric) arteries. shRNA knockdown of PLCγ1 and RISP; PLC inhibitor; IP3R antagonists; Ca²⁺ imaging; IP3 measurement; isolated pulmonary artery contraction American journal of physiology. Lung cellular and molecular physiology Medium 23204067
2014 PLCγ1 is activated downstream of EpoR-Jak2 (independently of Stat5) and is required for erythropoiesis: PLCγ1-deficient erythroid progenitors show impaired differentiation and colony-forming potential in vitro and in vivo; the top downstream effector identified is the histone variant macroH2A2 (encoded by H2afy2), whose inactivation recapitulates PLCγ1 depletion effects on erythroid maturation. Plcγ1 loss-of-function in HSCs; colony assays; flow cytometry; in vivo reconstitution; transcriptomic and DNA methylation analyses; macroH2A2 knockdown Cell death and differentiation Medium 25394487
2015 CD47 agonist peptides induce Ca²⁺-mediated, caspase-independent programmed cell death in CLL B cells through sustained phosphorylation of PLCγ1 at Y783; downregulation of PLCγ1 or pharmacological inhibition of PLCγ1 phosphorylation abolishes CD47-mediated killing. siRNA knockdown and pharmacological inhibition of PLCγ1; Ca²⁺ flux assays; cell death assays; xenograft mouse model PLoS medicine Medium 25734483
2023 A de novo germline PLCG1 S1021F variant is a gain-of-function mutation causing immune dysregulation: it leads to increased IP3 production, intracellular Ca²⁺ release, and enhanced phosphorylation of ERK, p65, and p38; it activates NF-κB and type II IFN pathways in T cells and NF-κB and type I IFN pathways in monocytes; PLCγ1 inhibitor or JAK inhibitor reverses the upregulated gene expression. Whole exome sequencing; IP-One ELISA for IP3; Ca²⁺ flux assay; immunoblotting; luciferase reporter; single-cell RNA-seq; pharmacological inhibitor reversal in patient cells and cell lines The Journal of allergy and clinical immunology High 37422272
2022 PLCG1 is required for AML1-ETO leukemic stem cell self-renewal; AE fusion protein induces PLCG1 expression by binding intergenic regulatory DNA elements; genetic inactivation of PLCG1 in murine and human AML inhibits AE-dependent self-renewal, proliferation, and leukemia maintenance in vivo; PLCG1 is dispensable for normal hematopoietic stem and progenitor cell function. Genetic inactivation of PLCG1; in vivo leukemia maintenance assays; normal HSC function assays; ChIP-seq identification of AE binding at PLCG1 regulatory elements; pharmacological Ca²⁺ signaling perturbation Blood High 34695195
2020 PLCγ1 suppression in KRAS-mutant lung adenocarcinoma cells during hypoxia promotes glycolytic metabolism by impairing Ca²⁺ entry into mitochondria, reducing mitochondrial ROS, preventing lipid peroxidation, and antagonizing apoptosis; loss of function of Plcg1 in KrasG12D-driven mouse lung adenocarcinoma increases glycolytic gene expression and boosts tumor growth. Lipidomic screen; PLCγ1 loss-of-function in cell lines; KrasG12D mouse model; mitochondrial Ca²⁺ and ROS measurements; metabolic assays Nature cell biology High 33077911
2024 PLCG1 is a substrate for chaperone-mediated autophagy (CMA): aberrant accumulation of PLCG1 caused by CMA blockage (LAMP2A reduction) results in calcium overload and induces nucleus pulposus cell senescence; knockdown of Plcg1 inhibits TNF-induced disc degeneration in rats. Structural and functional proteomic screens; immunoprecipitation; calcium flux assays; LAMP2A overexpression and Plcg1 knockdown in rat disc degeneration model; immunoassays on human specimens Autophagy Medium 39212196
2020 NDRG1 forms a complex with PLCγ1 through NDRG1 phosphorylation sites and is required for VEGF-A-induced PLCγ1 and ERK1/2 activation in endothelial cells; Ndrg1−/− mice exhibit impaired VEGF-A-induced angiogenesis without affecting VEGFR2 expression or function, placing NDRG1 upstream of PLCγ1 in the VEGF-A angiogenic pathway. Co-immunoprecipitation; Ndrg1 knockout mice; corneal angiogenesis assay; PLCγ1 and ERK1/2 phosphorylation assays; aortic sprouting assay Communications biology Medium 32144393
2012 Kaposi's sarcoma herpesvirus K15 protein directly recruits PLCγ1, activating calcineurin/NFAT1-dependent RCAN1 expression and promoting angiogenic tube formation; deletion or siRNA silencing of K15 abrogates these effects. Co-immunoprecipitation; NFAT luciferase reporter; siRNA knockdown; angiogenic tube formation assay; KSHV K15 deletion mutant PLoS pathogens Medium 23028325
2011 Phospho-STAT3 (Y705) directly associates with PLCγ1 in colorectal cancer cells; PLCγ1 activity is reduced in STAT3 Y705F mutant cells; overexpression of constitutively active PLCγ1 rescues the transformation defect of STAT3 Y705F mutant cells, establishing a functional STAT3-PLCγ1 cross-talk in colorectal tumorigenesis. STAT3 Y705F knock-in; co-immunoprecipitation; constitutively active PLCγ1 rescue; colony and xenograft assays Molecular cancer research : MCR Medium 21840932
2009 Molecular genetic analysis of FGFR1 signaling demonstrates that PLCγ1 activation downstream of FGFR1 is integral to maintenance of adult neural stem cell characteristics (capacity for neuronal and oligodendroglial differentiation), whereas the MAPK/Erk1/2 pathway is required and sufficient for NSC expansion and anti-differentiation. Molecular genetic approach using FGFR1 cytoplasmic residue mutants that selectively disrupt MAPK or PLC activation; adult rat NSC culture; proliferation and differentiation assays Molecular brain Medium 19505325
2013 PLC-γ1 activation is required for postbinding cell entry of influenza H1N1 (but not H3N2); H1N1 infection induces phosphorylation of PLCγ1 at Ser1248 immediately after infection downstream of EGFR; both pharmacological inhibition and shRNA knockdown of PLCγ1 suppress H1N1 replication. PLC-γ1-specific inhibitor; shRNA knockdown; PLCγ1 Ser1248 phosphorylation assay; viral replication assays; EGFR epistasis Journal of virology Medium 24155396
2002 PLC-γ1 enzyme activity is required for insulin-induced DNA synthesis in hIRcB fibroblasts; the insulin receptor physically associates with PLCγ1; disruption of this interaction by microinjection of SH2 domains blocks mitogenesis; the requirement for PLC-γ1 is specifically for its lipase activity producing DAG (rescued by synthetic DAG but not IP3). PLC activity inhibitor; microinjection of SH2 domain peptides and neutralizing antibodies; DNA synthesis assay; DAG/IP3 rescue experiments Endocrinology Medium 11796522
2002 PLCγ1 is required for IGF-I-dependent cell survival in suspension (anoikis protection); IGF-I rescues Null+ but not Null (Plcg1−/−) cells from suspension-induced apoptosis; IGF-I stimulates PLCγ1 tyrosine phosphorylation in both adherent and suspension cells. Plcg1−/− and re-expressed (Null+) fibroblasts; suspension-induced cell death assay; caspase-3 activity; PLCγ1 tyrosine phosphorylation assay Journal of cell science Medium 11973363
2015 PLCγ2 cSH2 domain binds K15 (KSHV) and acts as a dominant-negative inhibitor of the K15P-PLCγ1 interaction; K15P-dependent PLCγ1 phosphorylation, NFAT-dependent promoter activation, and invasiveness/angiogenesis of KSHV-infected cells are abrogated by this domain; two amino acid substitutions enhance its inhibitory potency. Domain mapping of PLCγ1/PLCγ2 interactions with K15; co-immunoprecipitation; dominant-negative expression; NFAT reporter; invasion and angiogenesis assays PLoS pathogens Medium 26295810
1997 Villin (ileal microvillar actin-binding protein) is tyrosine-phosphorylated and associates with PLCγ1 in brush border membrane; carbachol increases this association and tyrosine phosphorylation of villin; F-actin stabilization prevents carbachol-induced NaCl absorption inhibition, linking PLCγ1/villin-mediated cytoskeletal rearrangement to NaCl absorption regulation. Co-immunoprecipitation of villin and PLCγ1; Triton fractionation; tyrosine phosphorylation assays; jasplakinolide F-actin stabilization; NaCl absorption assay The Journal of biological chemistry Medium 9374490
2020 EphA2 receptor tyrosine kinase interacts with PLCγ1 (identified by yeast two-hybrid screen); EphA2 kinase activity is required for PLCγ1 phosphorylation; genetic or pharmacologic inhibition of EphA2 decreases PLCγ1 phosphorylation; CRISPR knockout of PLCγ1 impairs tumor growth in vitro and in a KrasG12D-p53-Lkb1 mouse lung tumor model. Yeast two-hybrid screen; co-immunoprecipitation; kinase inhibition; CRISPR PLCγ1 knockout; in vivo mouse lung tumor model Molecular cancer research : MCR Medium 32753469
2018 PLCγ1 (phosphorylated at Y783) is activated by hypoxia through ROS-dependent signaling, generating IP3 that promotes PKCε activation, IP3R1 opening, Ca²⁺ release, and contraction in pulmonary artery smooth muscle cells; chronic hypoxia enhances PLCγ1 expression and activity in PASMCs, contributing to pulmonary hypertension. H2O2-induced PLCγ1 Y783 phosphorylation assay; PKCε knockout PASMCs; IP3R1 knockdown; IP3 production assay; Ca²⁺ imaging; pulmonary artery contraction assay American journal of physiology. Lung cellular and molecular physiology Medium 29388468
2014 TCR-mediated PLCγ1 activation is induced at LAT (simultaneous onset of LAT Y132 and PLCγ1 Y783 phosphorylation); PLCγ1 activation occurs more rapidly than LAT Y132 phosphorylation; the LAT-PLCγ1 association is more transient than LAT-Grb2; a pool of activated PLCγ1 translocates away from LAT to TCR-containing cellular structures. Phosphorylation kinetics analysis; co-immunoprecipitation; imaging of activated PLCγ1 localization at LAT vs. TCR complexes Cellular signalling Medium 24412752
2018 Cish SH2 domain binding to PLCγ1 is essential for PLCγ1 ubiquitination and degradation; Cish SH2 domain is required for Cish-mediated inhibition of Ca²⁺ release upon TCR stimulation; Cish is expressed mostly in the cytoplasm and does not cluster at the plasma membrane upon stimulation. Cish SH2 domain mutants (R107K) and D/BC domain mutants; PLCγ1 ubiquitination assay; Ca²⁺ flux assay; cytokine measurements; imaging of Cish localization Scientific reports Medium 29593227

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 LAT is required for TCR-mediated activation of PLCgamma1 and the Ras pathway. Immunity 407 9846483
2014 Recurrent PTPRB and PLCG1 mutations in angiosarcoma. Nature genetics 258 24633157
2014 PLCG1 mutations in cutaneous T-cell lymphomas. Blood 177 24497536
2010 miR-200bc/429 cluster targets PLCgamma1 and differentially regulates proliferation and EGF-driven invasion than miR-200a/141 in breast cancer. Oncogene 175 20514023
2012 F-actin polymerization and retrograde flow drive sustained PLCγ1 signaling during T cell activation. The Journal of cell biology 168 22665519
2016 Recurrent CIC Gene Abnormalities in Angiosarcomas: A Molecular Study of 120 Cases With Concurrent Investigation of PLCG1, KDR, MYC, and FLT4 Gene Alterations. The American journal of surgical pathology 165 26735859
2001 Identification of a phospholipase C-gamma1 (PLC-gamma1) SH3 domain-binding site in SLP-76 required for T-cell receptor-mediated activation of PLC-gamma1 and NFAT. Molecular and cellular biology 164 11390650
1993 The putative phosphoinositide-specific phospholipase C gene, PLC1, of the yeast Saccharomyces cerevisiae is important for cell growth. Proceedings of the National Academy of Sciences of the United States of America 144 8383328
2001 Absence of erythrogenesis and vasculogenesis in Plcg1-deficient mice. The Journal of biological chemistry 120 11744703
2005 VEGF-PLCgamma1 pathway controls cardiac contractility in the embryonic heart. Genes & development 114 15998812
2009 A genetic screen for vascular mutants in zebrafish reveals dynamic roles for Vegf/Plcg1 signaling during artery development. Developmental biology 111 19269286
2014 A PLCγ1-dependent, force-sensitive signaling network in the myogenic constriction of cerebral arteries. Science signaling 109 24866019
2019 Artesunate attenuates LPS-induced osteoclastogenesis by suppressing TLR4/TRAF6 and PLCγ1-Ca2+-NFATc1 signaling pathway. Acta pharmacologica Sinica 108 31431733
2000 Pleiotropic contributions of phospholipase C-gamma1 (PLC-gamma1) to T-cell antigen receptor-mediated signaling: reconstitution studies of a PLC-gamma1-deficient Jurkat T-cell line. Molecular and cellular biology 107 11094067
2011 Aging and a peripheral immune challenge interact to reduce mature brain-derived neurotrophic factor and activation of TrkB, PLCgamma1, and ERK in hippocampal synaptoneurosomes. The Journal of neuroscience : the official journal of the Society for Neuroscience 106 21411668
2006 Recruitment and activation of PLCgamma1 in T cells: a new insight into old domains. The EMBO journal 103 16467851
2003 A new link between the c-Abl tyrosine kinase and phosphoinositide signalling through PLC-gamma1. Nature cell biology 103 12652307
2005 PLCgamma1 is essential for early events in integrin signalling required for cell motility. Journal of cell science 93 15944397
1993 A mutation in PLC1, a candidate phosphoinositide-specific phospholipase C gene from Saccharomyces cerevisiae, causes aberrant mitotic chromosome segregation. Molecular and cellular biology 89 8391635
2003 Murine GPVI stimulates weak integrin activation in PLCgamma2-/- platelets: involvement of PLCgamma1 and PI3-kinase. Blood 85 12730118
1998 Wortmannin-sensitive phosphorylation, translocation, and activation of PLCgamma1, but not PLCgamma2, in antigen-stimulated RBL-2H3 mast cells. Molecular biology of the cell 84 9450969
2011 A phenomics-based strategy identifies loci on APOC1, BRAP, and PLCG1 associated with metabolic syndrome phenotype domains. PLoS genetics 80 22022282
2015 CD47 agonist peptides induce programmed cell death in refractory chronic lymphocytic leukemia B cells via PLCγ1 activation: evidence from mice and humans. PLoS medicine 66 25734483
2014 A recurrent activating PLCG1 mutation in cardiac angiosarcomas increases apoptosis resistance and invasiveness of endothelial cells. Cancer research 64 25252913
2009 PLC-gamma1 and Rac1 coregulate EGF-induced cytoskeleton remodeling and cell migration. Molecular endocrinology (Baltimore, Md.) 64 19264842
1998 Epidermal growth factor signaling and mitogenesis in Plcg1 null mouse embryonic fibroblasts. Molecular biology of the cell 64 9529375
2017 7,8-dihydroxyflavone ameliorates cognitive and motor deficits in a Huntington's disease mouse model through specific activation of the PLCγ1 pathway. Human molecular genetics 58 28541476
2017 PLCγ1: Potential arbitrator of cancer progression. Advances in biological regulation 56 29174396
2009 Molecular genetic analysis of FGFR1 signalling reveals distinct roles of MAPK and PLCgamma1 activation for self-renewal of adult neural stem cells. Molecular brain 56 19505325
2007 A critical role for the E3-ligase activity of c-Cbl in VEGFR-2-mediated PLCgamma1 activation and angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 56 17372230
2004 Positive feedback regulation of PLCgamma1/Ca(2+) signaling by PKCtheta in restimulated T cells via a Tec kinase-dependent pathway. European journal of immunology 56 15214048
2021 PLCγ1 promotes phase separation of T cell signaling components. The Journal of cell biology 55 33929486
2012 Kaposi's sarcoma herpesvirus K15 protein contributes to virus-induced angiogenesis by recruiting PLCγ1 and activating NFAT1-dependent RCAN1 expression. PLoS pathogens 50 23028325
2003 Tr-kit promotes the formation of a multimolecular complex composed by Fyn, PLCgamma1 and Sam68. Oncogene 50 14647465
2016 Artesunate suppresses RANKL-induced osteoclastogenesis through inhibition of PLCγ1-Ca2+-NFATc1 signaling pathway and prevents ovariectomy-induced bone loss. Biochemical pharmacology 48 27789216
2024 Impaired degradation of PLCG1 by chaperone-mediated autophagy promotes cellular senescence and intervertebral disc degeneration. Autophagy 46 39212196
2005 Integrin-dependent PLC-gamma1 phosphorylation mediates fibronectin-dependent adhesion. Journal of cell science 45 15657076
2001 The phospholipase C-gamma1 gene (PLCG1) and lithium-responsive bipolar disorder: re-examination of an intronic dinucleotide repeat polymorphism. Psychiatric genetics 45 11409699
2012 A novel regulatory mechanism links PLCγ1 to PDK1. Journal of cell science 42 22454520
1999 Lysophosphatidylcholine activates mesangial cell PKC and MAP kinase by PLCgamma-1 and tyrosine kinase-Ras pathways. The American journal of physiology 42 10484515
2009 VEGFR2-PLCgamma1 axis is essential for endothelial specification of VEGFR2+ vascular progenitor cells. Journal of cell science 41 19706681
2003 EGF-stimulated signaling by means of PI3K, PLCgamma1, and PKC isozymes regulates branching morphogenesis of the fetal mouse submandibular gland. Developmental dynamics : an official publication of the American Association of Anatomists 40 12761849
2021 Emerging roles of PLCγ1 in endothelial biology. Science signaling 39 34344833
2014 Competition between Grb2 and Plcγ1 for FGFR2 regulates basal phospholipase activity and invasion. Nature structural & molecular biology 39 24440983
2013 PLC-γ1 signaling plays a subtype-specific role in postbinding cell entry of influenza A virus. Journal of virology 38 24155396
2001 EGF-dependent translocation of green fluorescent protein-tagged PLC-gamma1 to the plasma membrane and endosomes. Experimental cell research 37 11412035
2000 The invasion protein InIB from Listeria monocytogenes activates PLC-gamma1 downstream from PI 3-kinase. Cellular microbiology 37 11207601
1997 Ileal microvillar protein villin is tyrosine-phosphorylated and associates with PLC-gamma1. Role of cytoskeletal rearrangement in the carbachol-induced inhibition of ileal NaCl absorption. The Journal of biological chemistry 33 9374490
2020 NDRG1 activates VEGF-A-induced angiogenesis through PLCγ1/ERK signaling in mouse vascular endothelial cells. Communications biology 32 32144393
2018 PLCγ1-PKCε-IP3R1 signaling plays an important role in hypoxia-induced calcium response in pulmonary artery smooth muscle cells. American journal of physiology. Lung cellular and molecular physiology 32 29388468
2018 Netrin-1/DCC-mediated PLCγ1 activation is required for axon guidance and brain structure development. EMBO reports 32 30224412
2014 Epo-induced erythroid maturation is dependent on Plcγ1 signaling. Cell death and differentiation 32 25394487
2012 Important role of PLC-γ1 in hypoxic increase in intracellular calcium in pulmonary arterial smooth muscle cells. American journal of physiology. Lung cellular and molecular physiology 32 23204067
2009 Memo is a cofilin-interacting protein that influences PLCgamma1 and cofilin activities, and is essential for maintaining directionality during ErbB2-induced tumor-cell migration. Journal of cell science 32 19223396
2011 Cross-talk between phospho-STAT3 and PLCγ1 plays a critical role in colorectal tumorigenesis. Molecular cancer research : MCR 31 21840932
2018 Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation. Nature chemical biology 30 30429604
2011 LKB1 regulates TCR-mediated PLCγ1 activation and thymocyte positive selection. The EMBO journal 30 21487392
2009 Itk tyrosine kinase substrate docking is mediated by a nonclassical SH2 domain surface of PLCgamma1. Proceedings of the National Academy of Sciences of the United States of America 29 19955438
2023 A gain-of-function variation in PLCG1 causes a new immune dysregulation disease. The Journal of allergy and clinical immunology 28 37422272
2020 FGFR1 Is Critical for RBL2 Loss-Driven Tumor Development and Requires PLCG1 Activation for Continued Growth of Small Cell Lung Cancer. Cancer research 28 32973083
2015 Phospholipase C gamma 1 (PLCG1) R707Q mutation is counterselected under targeted therapy in a patient with hepatic angiosarcoma. Oncotarget 28 26474454
2016 A Small Molecule Inhibitor of PDK1/PLCγ1 Interaction Blocks Breast and Melanoma Cancer Cell Invasion. Scientific reports 27 27199173
2015 DAG/PKCδ and IP3/Ca²⁺/CaMK IIβ Operate in Parallel to Each Other in PLCγ1-Driven Cell Proliferation and Migration of Human Gastric Adenocarcinoma Cells, through Akt/mTOR/S6 Pathway. International journal of molecular sciences 26 26633375
2014 PLCγ1-PKCγ signaling-mediated Hsp90α plasma membrane translocation facilitates tumor metastasis. Traffic (Copenhagen, Denmark) 26 24899266
2014 PDGF regulates chondrocyte proliferation through activation of the GIT1- and PLCγ1-mediated ERK1/2 signaling pathway. Molecular medicine reports 26 25175053
2011 c-Cbl inhibits angiogenesis and tumor growth by suppressing activation of PLCγ1. Oncogene 26 21242968
2019 BDNF activates TrkB/PLCγ1 signaling pathway to promote proliferation and invasion of ovarian cancer cells through inhibition of apoptosis. European review for medical and pharmacological sciences 25 31298409
2019 Frequent and Persistent PLCG1 Mutations in Sézary Cells Directly Enhance PLCγ1 Activity and Stimulate NFκB, AP-1, and NFAT Signaling. The Journal of investigative dermatology 25 31376383
2015 GRB2 Nucleates T Cell Receptor-Mediated LAT Clusters That Control PLC-γ1 Activation and Cytokine Production. Frontiers in immunology 25 25870599
2015 Inhibiting the Recruitment of PLCγ1 to Kaposi's Sarcoma Herpesvirus K15 Protein Reduces the Invasiveness and Angiogenesis of Infected Endothelial Cells. PLoS pathogens 25 26295810
2009 EGFR-PLCgamma1 signaling mediates high glucose-induced PKCbeta1-Akt activation and collagen I upregulation in mesangial cells. American journal of physiology. Renal physiology 25 19605547
1995 Molecular cloning of the plc1+ gene of Schizosaccharomyces pombe, which encodes a putative phosphoinositide-specific phospholipase C. Yeast (Chichester, England) 25 7732727
1995 Isolation and characterization of temperature-sensitive plc1 mutants of the yeast Saccharomyces cerevisiae. Molecular & general genetics : MGG 25 7753023
2009 RIAM regulates the cytoskeletal distribution and activation of PLC-gamma1 in T cells. Science signaling 24 19952372
2020 PLCγ1 suppression promotes the adaptation of KRAS-mutant lung adenocarcinomas to hypoxia. Nature cell biology 23 33077911
2018 The Cish SH2 domain is essential for PLC-γ1 regulation in TCR stimulated CD8+ T cells. Scientific reports 22 29593227
2009 Caenorhabditis elegans FOS-1 and JUN-1 regulate plc-1 expression in the spermatheca to control ovulation. Molecular biology of the cell 22 19570917
2016 Inducible costimulator (ICOS) potentiates TCR-induced calcium flux by augmenting PLCγ1 activation and actin remodeling. Molecular immunology 21 27693916
2015 The Involvement of Mutual Inhibition of ERK and mTOR in PLCγ1-Mediated MMP-13 Expression in Human Osteoarthritis Chondrocytes. International journal of molecular sciences 21 26247939
2022 PLCG1 is required for AML1-ETO leukemia stem cell self-renewal. Blood 20 34695195
2015 Reduced expression of E-cadherin and p120-catenin and elevated expression of PLC-γ1 and PIKE are associated with aggressiveness of oral squamous cell carcinoma. International journal of clinical and experimental pathology 20 26464646
1992 A microsatellite polymorphism associated with the PLC1 (phospholipase C) locus: identification, mapping, and linkage to the MODY locus on chromosome 20. Genomics 20 1639386
2023 BPTF Drives Gastric Cancer Resistance to EGFR Inhibitor by Epigenetically Regulating the C-MYC/PLCG1/Perk Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 18 37863665
2020 PLCγ1 inhibition-driven autophagy of IL-1β-treated chondrocyte confers cartilage protection against osteoarthritis, involving AMPK, Erk and Akt. Journal of cellular and molecular medicine 18 33372388
2015 Scaffold Protein SLP-76 Primes PLCγ1 for Activation by ITK-Mediated Phosphorylation. Journal of molecular biology 18 25916191
2011 Periodic mechanical stress activates MEK1/2-ERK1/2 mitogenic signals in rat chondrocytes through Src and PLCγ1. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 18 22068908
2002 PLC-gamma1 is required for IGF-I protection from cell death induced by loss of extracellular matrix adhesion. Journal of cell science 18 11973363
2023 Rosmarinic acid ameliorates skin inflammation and pruritus in allergic contact dermatitis by inhibiting mast cell-mediated MRGPRX2/PLCγ1 signaling pathway. International immunopharmacology 17 36931000
2012 Periodic mechanical stress activates integrinβ1-dependent Src-dependent PLCγ1-independent Rac1 mitogenic signal in rat chondrocytes through ERK1/2. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 17 22890232
2002 Angiotensin II stimulates calcineurin activity in proximal tubule epithelia through AT-1 receptor-mediated tyrosine phosphorylation of the PLC-gamma1 isoform. Journal of the American Society of Nephrology : JASN 17 12089370
2020 Dark Sweet Cherry (Prunus avium) Phenolics Enriched in Anthocyanins Induced Apoptosis in MDA-MB-453 Breast Cancer Cells through MAPK-Dependent Signaling and Reduced Invasion via Akt and PLCγ-1 Downregulation. Nutrition and cancer 16 32924599
2015 Antiproliferative Activity of Hinokitiol, a Tropolone Derivative, Is Mediated via the Inductions of p-JNK and p-PLCγ1 Signaling in PDGF-BB-Stimulated Vascular Smooth Muscle Cells. Molecules (Basel, Switzerland) 16 25961161
2010 Periodic mechanical stress enhances rat chondrocyte area expansion and migration through Src-PLCgamma1-ERK1/2 signaling. European journal of cell biology 16 20537760
2002 PLC-gamma1 enzyme activity is required for insulin-induced DNA synthesis. Endocrinology 16 11796522
2020 Phosphorylation of PLCγ1 by EphA2 Receptor Tyrosine Kinase Promotes Tumor Growth in Lung Cancer. Molecular cancer research : MCR 15 32753469
2014 Activated PLC-γ1 is catalytically induced at LAT but activated PLC-γ1 is localized at both LAT- and TCR-containing complexes. Cellular signalling 15 24412752
2012 MHO1, an evolutionarily conserved gene, is synthetic lethal with PLC1; Mho1p has a role in invasive growth. PloS one 15 22412880
1998 Fibroblast growth factor 2 uses PLC-gamma1 for cell proliferation and PI3-kinase for alteration of cell shape and cell proliferation in corneal endothelial cells. Molecular vision 15 9808840
1995 Phospholipase C gamma-2 (Plcg2) and phospholipase C gamma-1 (Plcg1) map to distinct regions in the human and mouse genomes. Genomics 15 7774933
2020 Nepetin, a natural compound from Inulae flos, suppresses degranulation and eicosanoid generation through PLCγ1 and Akt signaling pathways in mast cells. Archives of pharmacal research 14 32016828

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