Affinage

Showing GP6 — GPVI is a alias.

GP6

Platelet glycoprotein VI · UniProt Q9HCN6

Length
339 aa
Mass
36.9 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 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

GP6 encodes GPVI, an immunoglobulin-superfamily collagen receptor expressed early during megakaryocyte differentiation and on platelets, where it functions as the principal activating receptor for collagen and related vascular ligands and as a driver of platelet adhesion, activation, and procoagulant responses (PMID:11278467, PMID:11723134). GPVI couples to the FcRγ chain via a transmembrane arginine and intracellular C-terminal tail, and upon ligand-induced clustering, Src-family kinases phosphorylate the FcRγ ITAM tyrosines, recruiting and activating Syk and culminating in PLCγ2 activation (PMID:11152687, PMID:20345705). Receptor avidity is achieved through dimerization and higher-order clustering: dimeric GPVI binds fibrous collagen with high affinity, while pre-existing dimers coalesce into actin cytoskeleton-dependent clusters on collagenous substrates that colocalize with phosphotyrosine signaling (PMID:12356768, PMID:28058806), and a domain-swapped dimer conformation mediated by a D2 C-C' loop hinge is structurally required for signaling independent of ligand binding (PMID:33512486). Beyond collagen, GPVI is a signaling receptor for laminin, EMMPRIN/CD147, globular adiponectin, hemin, fibrin and the fibrinogen αC-region, and snake venom proteins such as convulxin and alborhagin, each triggering the FcRγ–Syk–PLCγ2 cascade (PMID:11344165, PMID:16219796, PMID:19350111, PMID:26282541, PMID:18419742, PMID:33472402, PMID:33843987). The proximal signal is shaped by a constitutive GPVI proline-rich-domain interaction with Lyn (PMID:19940238), by c-Cbl-mediated ubiquitination that enhances Syk activity, and by TULA-2 dephosphorylation of Syk Tyr346 (PMID:15701717, PMID:27609517), with downstream propagation through LAT, SLP-76, Tec/Btk kinases, FAK, Cdc42, and Nox1-derived ROS to control granule secretion, integrin αIIbβ3 activation, and phosphatidylserine exposure (PMID:10567557, PMID:12842985, PMID:21789221, PMID:24494191, PMID:25415317). GPVI surface levels are governed by ADAM10/ADAM17-mediated ectodomain shedding and by receptor internalization, both operating downstream of the FcRγ ITAM, while GP6 transcription is initiated by TPO-driven CpG demethylation of its promoter during megakaryopoiesis (PMID:15701720, PMID:17374738, PMID:20644114). A homozygous GP6 frameshift producing a truncated protein lacking the transmembrane domain ablates surface GPVI and collagen responsiveness, causing a mild bleeding diathesis (PMID:23815599, PMID:32603422). GPVI also extends beyond hemostasis to inflammation, promoting platelet-neutrophil complex formation and NETosis in acute lung injury (PMID:37441848).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Established that the platelet collagen receptor p62/GPVI transduces collagen-like activation, defining a Src-kinase-to-Syk phosphorylation cascade through the FcRγ chain.

    Evidence Convulxin binding and tyrosine-phosphorylation cascade mapping in platelet lysates with kinase inhibitor

    PMID:9153205

    Open questions at the time
    • Did not establish the receptor's quaternary state
    • Direct collagen-binding site not yet mapped
  2. 2001 High

    Defined the structural requirements for GPVI–FcRγ coupling and demonstrated that GPVI density determines collagen adhesion and signaling, while showing GPVI is functional from early megakaryopoiesis.

    Evidence Reconstitution in RBL-2H3/K562/Jurkat cells with transmembrane and C-tail mutagenesis, density-titrated cell lines, and megakaryocyte differentiation assays

    PMID:11152687 PMID:11278467 PMID:11344165 PMID:11723134

    Open questions at the time
    • Whether GPVI signals as monomer or dimer unresolved
    • Relationship to α2β1 in collagen binding not yet defined
  3. 2002 High

    Resolved that GPVI dimerization, not the monomer, confers high-affinity collagen binding and that the convulxin and collagen sites are distinct, establishing avidity as central to receptor function.

    Evidence SPR kinetics and aggregation-inhibition assays comparing monomeric and dimeric recombinant GPVI ectodomains

    PMID:12356768

    Open questions at the time
    • Dimer existence on native platelets inferred, not yet imaged
    • Structural basis of dimerization unknown
  4. 2005 High

    Built the downstream signaling map by ordering LAT, SLP-76, Tec/Btk, and PLCγ1/γ2 contributions and defining differential adaptor requirements relative to TCR signaling.

    Evidence Genetic knockout mouse platelets (LAT, SLP-76, Syk, Btk/Tec, PLCγ2, FcRγ) with epistasis and functional readouts; XLA human platelets

    PMID:10567557 PMID:11901197 PMID:12730118 PMID:12842985

    Open questions at the time
    • Species differences in PLCγ1 compensation not mechanistically explained
    • Quantitative contribution of minor LAT-independent branch unclear
  5. 2005 High

    Identified post-translational control points of proximal signaling — c-Cbl-dependent Syk ubiquitination enhancing kinase activity — and the cooperative role of α2β1 in increasing collagen avidity.

    Evidence c-Cbl-/- platelets with ubiquitin-IP and in vitro kinase assays; pharmacological α2β1/ADP/COX dissection under flow

    PMID:12871331 PMID:15701717 PMID:15886326

    Open questions at the time
    • Mechanism by which ubiquitination raises Syk activity not fully resolved
    • α2β1 avidity role established largely pharmacologically
  6. 2005 High

    Connected GPVI transcriptional control and ligand repertoire expansion, showing TPO-driven promoter demethylation drives GP6 expression and GPVI serves as a laminin receptor.

    Evidence Bisulfite sequencing with TPO treatment; GPVI-/- and Syk-/- platelets, α6 blockade, and SPR for laminin binding

    PMID:15701720 PMID:16219796

    Open questions at the time
    • Transcription factors acting on the demethylated promoter not identified
    • Laminin-binding site on GPVI not mapped
  7. 2007 High

    Defined the regulation of GPVI surface expression, distinguishing ADAM-mediated ectodomain shedding from internalization, both downstream of the FcRγ ITAM.

    Evidence MALDI-TOF-MS peptide cleavage, ADAM10/ADAM17 enzyme assays, and FcRγ ITAM point-mutant, LAT-/-, and PLCγ2-/- mice with flow cytometry

    PMID:17374738 PMID:17445093

    Open questions at the time
    • In vivo dominant sheddase not yet pinned down in this work
    • Signals rendering GPVI susceptible to cleavage incompletely defined
  8. 2009 High

    Characterized the proximal signaling architecture — constitutive Lyn priming via the GPVI proline-rich domain, tetraspanin microdomain localization, and Lyn/PKCδ/SHIP-1 negative regulation of secretion.

    Evidence Reciprocal Co-IP, PRD-deletion mutants, Lyn-/-/SHIP-1-/-/PKCδ-/- platelets, and Tspan9 Co-IP/colocalization

    PMID:18795891 PMID:19587372 PMID:19940238

    Open questions at the time
    • Tetraspanin microdomain functional consequence rests on single-lab Co-IP
    • How Lyn-priming integrates with negative SHIP-1 regulation temporally unclear
  9. 2009 High

    Expanded the GPVI ligand repertoire to EMMPRIN, globular adiponectin, and an alborhagin venom protein, and informed collagen recognition through the homologous LAIR-1 structure.

    Evidence SPR/ELISA binding with transfected CHO/Jurkat reporters, FcRγ-/- platelets, and LAIR-1 crystallography with NMR and mutagenesis

    PMID:18419742 PMID:19350111 PMID:20007810 PMID:20040043

    Open questions at the time
    • Physiological relevance of EMMPRIN and adiponectin engagement in vivo not established
    • Conserved collagen-contact residues inferred from a homolog, not GPVI structure
  10. 2014 High

    Extended the downstream effector network to Cdc42, FAK, Nox1-derived ROS, and identified CEACAM2 as an ITIM-bearing negative regulator of GPVI signaling.

    Evidence Inducible Cdc42 knockout, Pyk2-/- platelets with FAK inhibitor, Nox2-/- with Nox1 inhibitor, and Ceacam2-/- platelets with in vivo thrombosis models

    PMID:21789221 PMID:24494191 PMID:25085348 PMID:25415317

    Open questions at the time
    • FAK pathway position rests partly on inhibitor epistasis from a single lab
    • Mechanism of CEACAM2 recruitment to GPVI not detailed
  11. 2017 High

    Established fibrin and fibrinogen as GPVI ligands and resolved the spatial mechanism of activation as actin-dependent clustering of pre-existing dimers.

    Evidence GPVI-/- mouse and GPVI-deficient human platelets, SPR fragment mapping (D-dimer, αC-region), and dSTORM/TIRF imaging of dimer clusters

    PMID:26282541 PMID:28058806 PMID:29296791

    Open questions at the time
    • Differential monomer vs dimer preference for fibrin vs collagen mechanistically incomplete
    • Link between cluster geometry and ITAM phosphorylation kinetics not quantified
  12. 2020 High

    Confirmed the physiological consequence of GPVI loss in humans and mapped the genome-wide phosphosignaling output including a TAK1-Rab7 endolysosomal branch.

    Evidence Homozygous GP6 loss-of-function human platelets under flow; TMT/SPS-MS3 phosphoproteomics with TAK1 inhibitor validation

    PMID:23815599 PMID:32603422 PMID:32640021

    Open questions at the time
    • Many phosphoproteomic relations remain individually unvalidated
    • Mechanism preserving partial adhesion despite GPVI loss not fully defined
  13. 2021 High

    Provided the structural and biophysical basis for GPVI signaling competence, defining the domain-swapped dimer via the D2 C-C' loop and the fibrinogen αC-region/avidity interaction.

    Evidence GPVI-Nb2 crystallography with C-C' loop truncation and NFAT reporter; multi-method binding with fibrinogen fragments, non-polymerizing fibrin variant, and hemin SPR

    PMID:33472402 PMID:33512486 PMID:33843987

    Open questions at the time
    • How domain-swapping is triggered by ligand clustering in the membrane unclear
    • Physiological role of hemin engagement in vivo not established
  14. 2023 High

    Demonstrated GPVI function beyond hemostasis, establishing its role in platelet-neutrophil complex formation and NETosis driving inflammatory injury.

    Evidence GPVI-deficient mice and anti-GPVI antibody in LPS-induced acute lung injury with intravital microscopy and NET quantification

    PMID:37441848

    Open questions at the time
    • GPVI ligand mediating neutrophil interactions in inflamed lung not identified
    • Whether the same FcRγ/Syk cascade drives the NETosis phenotype not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • The identity of the third in vivo GPVI-cleaving sheddase and the membrane-level trigger converting ligand clustering into domain-swapped, signaling-competent dimers remain open.
  • Third platelet GPVI sheddase beyond ADAM10/ADAM17 unidentified
  • Coupling between cluster geometry and the D2 domain-swap conformational change unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098631 cell adhesion mediator activity 4 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-109582 Hemostasis 4 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 1
Partners
CBLFCER1GITGA6LATLYNPLCG2SYKTSPAN9
Complex memberships
GPVI-FcRγ receptor complextetraspanin (Tspan9) microdomain

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 Convulxin, a C-type lectin from snake venom, activates platelets through the p62/GPVI collagen receptor (not GPIb), inducing tyrosine phosphorylation of FcRγ chain, PLCγ2, Syk (p72), c-Cbl, and p36-38 in a pattern similar to collagen. Convulxin binds directly to GPVI immunoprecipitated from platelet lysates, and convulxin subunits inhibit both aggregation and tyrosine phosphorylation in response to collagen. Src family kinases phosphorylate FcRγ chain upon GPVI clustering, activating Syk downstream. 125I-convulxin binding, immunoprecipitation, tyrosine phosphorylation western blot, platelet aggregation assay, tyrosine kinase inhibitor (piceatannol) The Journal of biological chemistry High 9153205
2001 GPVI expression in RBL-2H3 cells (which express FcRγ chain) confers adhesive and signaling responses to convulxin via the Fc receptor γ-chain. Both the transmembrane arginine of GPVI and its intracellular C-terminal tail are required for coupling to FcRγ and signal transduction. GPVI expression was sufficient for convulxin responses but not for full collagen signaling, suggesting an additional collagen-binding receptor is required. Transfection of wild-type and mutant GPVI into RBL-2H3 cells, adhesion assays, signaling readouts, mutagenesis of transmembrane domain and C-tail The Journal of biological chemistry High 11152687
2001 GPVI is expressed early during megakaryocyte differentiation (CD41+ stage) and associates with the FcRγ chain in megakaryocytes as in platelets. Functional GPVI-mediated signaling (tyrosine phosphorylation of Syk, FcRγ, PLCγ2) is activated by convulxin in mature megakaryocytes; adhesion to immobilized convulxin occurs only at late stages of maturation when GPVI expression increases. Flow cytometry, RT-PCR, immunoblotting, ligand blotting, adhesion assays, tyrosine phosphorylation analysis The Journal of biological chemistry High 11278467
2001 Alborhagin, a viper venom metalloproteinase, activates platelets through GPVI (not through a distinct receptor), inducing a tyrosine phosphorylation pattern similar to convulxin including PLCγ2 phosphorylation. Alborhagin-induced aggregation in mouse platelets is inhibited by anti-GPVI monoclonal antibody JAQ1, and alborhagin induces GPVI-dependent responses in GPVI-transfected K562 and Jurkat cells. Platelet aggregation, tyrosine phosphorylation western blot, transfected cell signaling, antibody inhibition (JAQ1), Src kinase inhibitor PP1 The Journal of biological chemistry High 11344165
2001 GPVI mediates both adhesive and signaling responses to collagen in a receptor density-dependent manner. GPVI-FcRγ expression alone is sufficient to confer collagen adhesion and signaling in RBL-2H3 cells when GPVI density matches that on human platelets; collagen responses are proportional to receptor density. GPVI receptor density on human platelets is tightly regulated and independent of α2β1 expression. Novel anti-GPVI monoclonal antibody quantification, GPVI-expressing RBL-2H3 cell lines at varying receptor densities, adhesion and signaling assays The Journal of biological chemistry High 11723134
2002 Dimeric GPVI (GPVI-Fc fusion) but not monomeric GPVI (GPVIex) exhibits high affinity binding to fibrous collagen (KD ~576 nM by SPR), inhibits collagen-induced platelet aggregation, and inhibits collagen-related peptide-induced aggregation. Monomeric GPVI inhibited convulxin- but not collagen-induced aggregation. The convulxin binding site on GPVI is distinct from the collagen-binding site. GPVI is proposed to exist as a dimeric form on platelets for high-affinity collagen interaction. ELISA, surface plasmon resonance (SPR), platelet aggregation inhibition assays with soluble monomeric and dimeric recombinant GPVI ectodomains The Journal of biological chemistry High 12356768
1999 LAT (linker for activation of T cells) is required for tyrosine phosphorylation of PLCγ2 downstream of the GPVI collagen receptor. LAT is tyrosine-phosphorylated downstream of Syk (not SLP-76 or Btk) following GPVI activation. In LAT-deficient platelets, PLCγ2 phosphorylation is substantially reduced, leading to marked inhibition of phosphatidic acid formation, pleckstrin phosphorylation, P-selectin expression, and reduced αIIbβ3 activation in response to CRP. A minor LAT-independent pathway of PLCγ2 phosphorylation exists. LAT-deficient mouse platelets, Syk-deficient mouse platelets, XLA human platelets (Btk-deficient), SLP-76-deficient mouse platelets, tyrosine phosphorylation western blot, metabolite measurement, flow cytometry Molecular and cellular biology High 10567557
2002 SLP-76 plays a greater role than LAT in platelet activation downstream of GPVI. LAT-deficient platelets aggregate normally to high concentrations of collagen and convulxin, while SLP-76-deficient platelets do not. LAT is not tyrosine-phosphorylated after fibrinogen binding to integrin αIIbβ3; collagen-stimulated LAT-deficient platelets spread normally on fibrinogen. These findings establish differential requirements for LAT and SLP-76 in GPVI versus TCR signaling. LAT-/- and SLP-76-/- mouse platelets, platelet aggregation, P-selectin expression, spreading assays, phosphorylation western blot The Journal of experimental medicine High 11901197
2003 Tec family kinase Tec compensates for Btk downstream of GPVI in regulating PLCγ2 phosphorylation. Btk/Tec double-deficient platelets fail to undergo Ca2+ increase, aggregation, secretion, and spreading in response to collagen or CRP, while single knockouts show partial defects. A residual GPVI signal persists in Btk/Tec double-deficient platelets as CRP synergizes with ADP to mediate aggregation. Btk-/-, Tec-/-, and Btk/Tec double-knockout mouse platelets, aggregation, Ca2+ measurement, secretion, spreading, PLCγ2 phosphorylation western blot Blood High 12842985
2003 Activation of GPVI by collagen is regulated by α2β1 integrin and secondary mediators (ADP, thromboxanes). α2β1 blockade has a greater inhibitory effect on collagen-induced PLC activation, Ca2+ elevation, and dense granule secretion than ADP receptor antagonists plus COX inhibitor. The major role of α2β1 is proposed to increase avidity of collagen for the platelet surface, thereby enhancing GPVI activation. Secondary mediators indirectly regulate GPVI signaling via activation of α2β1. Platelet aggregation, tyrosine phosphorylation, Ca2+ measurement, dense granule secretion with pharmacological inhibitors of α2β1, ADP receptors, and COX; integrin αIIbβ3 antagonist to isolate signaling from aggregation Journal of thrombosis and haemostasis Medium 12871331
2004 GPVI undergoes metalloproteinase-dependent ectodomain shedding generating a ~55 kDa soluble fragment released from platelets. This shedding is induced by mitochondrial injury (CCCP) and is inhibited by the broad-spectrum metalloproteinase inhibitor GM6001. CRP or thrombin stimulation induces shedding of GPIbα but not GPVI, suggesting different metalloproteinases regulate the two receptors or an additional signal is needed to render GPVI susceptible to cleavage. Mouse platelet stimulation with CCCP, GM6001 inhibition, immunoblotting of supernatant and lysate, platelet aggregation and CRP/thrombin response assays Thrombosis and haemostasis Medium 15116256
2005 GPVI is a receptor for laminin. Lamellipodia (but not filopodia) formation on laminin requires GPVI, as demonstrated in GPVI-knockout mouse platelets. Integrin α6β1 is essential for adhesion to laminin and brings laminin to GPVI. GPVI-laminin interaction was confirmed by surface plasmon resonance spectroscopy and by lamellipodia formation on laminin in the presence of collagenase. Syk kinase is required for signaling downstream of both GPVI and α6β1. GPVI-/- mouse platelets, α6-blocking antibody, Syk-/- mouse platelets, surface plasmon resonance, collagenase treatment, platelet spreading microscopy Blood High 16219796
2005 Both GPVI and integrin α2β1 play independent critical roles in platelet adhesion to collagen under flow; loss of both receptors completely ablates this response. Intracellular signaling mediated by SLP-76 (but not LAT) is critical for platelet adhesion to collagen under flow. Reduced GPVI receptor density results in severe defects in platelet adhesion to collagen under flow. Pharmacological and genetic approaches with human and mouse platelets under flow conditions; SLP-76-/- and LAT-/- mice; GPVI density variation; tail bleeding times Blood High 15886326
2005 Syk undergoes rapid ubiquitination upon GPVI activation by collagen, CRP, and convulxin; this process is downstream of Src family kinases. Ubiquitinated Syk is ~5-fold more kinase-active than non-ubiquitinated Syk and represents 60-75% of active (pTyr525/526) Syk. In c-Cbl-deficient mice, Syk is not ubiquitinated and fails to be dephosphorylated, implicating c-Cbl as the E3 ubiquitin ligase for Syk in GPVI signaling. c-Cbl-/- mouse platelets, Src kinase inhibitor, ubiquitin immunoprecipitation, in vitro kinase assay on separated ubiquitinated/non-ubiquitinated Syk, phosphospecific antibody to Syk Blood High 15701717
2005 Thrombopoietin (TPO) initiates CpG demethylation of the GP6 promoter, which drives GPVI transcription during megakaryocyte differentiation. The GP6 promoter CpG island is fully methylated in GPVI-non-expressive cell lines and completely unmethylated in GPVI-expressive lines. TPO treatment of UT-7/EPO-Mpl cells induces GP6 promoter demethylation correlated with increased mRNA. Sodium bisulfite genomic sequencing of CpG island, RT-PCR for mRNA quantification, TPO treatment of primary cord blood cells and cell lines Blood High 15701720
2004 Collagen type I-induced stress fiber formation in megakaryocytes requires α2β1 integrin (essential) and GPVI (triggers rapid and sustained ERK1/2 MAPK activation). Both pathways converge via synergistic MAPK/ERK1/2 and Rho/ROCK activation. After longer adhesion, proplatelet formation is inhibited by α2β1 but not by GPVI, through the Rho/ROCK pathway. This demonstrates differential regulation of megakaryocyte actin dynamics by the two collagen receptors. Function-blocking antibodies against α2β1 and GPVI-specific ligands in primary human megakaryocytes, kinase inhibitors (ROCK, ERK1/2), F-actin staining, proplatelet formation assay Blood High 15265786
2007 ADAM10, but not ADAM17, cleaves a GPVI-based synthetic peptide within the extracellular membrane-proximal sequence (PAR;Q243YY) as identified by MALDI-TOF-MS. GPVI and GPIbα are shed by distinct ADAM family members (ADAM10 for GPVI, ADAM17 for GPIbα) in response to distinct stimuli (CCCP, PMA, W7, NEM). A significant fraction of GPIbα but not GPVI exists in cleaved state on resting platelets. Immunoblotting with affinity-purified cytoplasmic domain antibodies, MALDI-TOF-MS of synthetic peptide cleavage products, ADAM10/ADAM17 recombinant enzyme assays, metalloproteinase inhibitors, mutagenesis of cleavage sequences in transfected cells Journal of thrombosis and haemostasis High 17445093
2007 GPVI down-regulation occurs through two distinct pathways downstream of the FcRγ-ITAM: ectodomain shedding (via metalloproteinases, requiring LAT and PLCγ2 signaling) or internalization/intracellular clearing (independent of shedding). Both pathways are abrogated in mice with a point mutation in the FcRγ ITAM. In LAT-/- or PLCγ2-/- mice, GPVI shedding is abolished but receptor is down-regulated through internalization without thrombocytopenia or altered thrombin responses. FcRγ ITAM point mutant mice, LAT-/- mice, PLCγ2-/- mice, anti-GPVI antibody (JAQ1) treatment, flow cytometry of GPVI surface levels, platelet count monitoring, thrombin response assays Blood High 17374738
2009 GPVI ectodomain shedding in vitro can be mediated by either ADAM10 or ADAM17 in response to distinct stimuli. In vivo antibody (JAQ1)-induced GPVI shedding occurs even in mice lacking both ADAM10 and ADAM17 in platelets, establishing the existence of a third GPVI-cleaving platelet enzyme. Megakaryocyte-specific ADAM10-deficient mice, Adam17ex/ex mice, ADAM10/ADAM17 double-deficient platelets in vitro and in vivo, anti-GPVI antibody JAQ1 treatment, flow cytometry Blood High 20644114
2009 GPVI constitutively associates in resting platelets with the Src-family kinase Lyn via a unique intracellular proline-rich domain (PRD), which directly activates Lyn presumably through SH3 displacement. Lyn is bound to GPVI in an activated state. Platelets lacking Lyn exhibit defective collagen adhesion under flow similar to platelets with GPVI receptors lacking the PRD. This PRD-Lyn interaction constitutes a molecular priming mechanism enabling rapid hemostatic response. Co-immunoprecipitation of Lyn with GPVI, PRD deletion mutant GPVI, Lyn-/- mouse platelets, platelet adhesion to collagen under flow, in vitro binding assays Proceedings of the National Academy of Sciences of the United States of America High 19940238
2009 GPVI is a component of tetraspanin microdomains on platelets, specifically associating with Tspan9 and integrin α6β1, but not with GPIbα or integrins αIIbβ3 or α2β1. This selective tetraspanin microdomain association was established by Co-IP and co-localization. Co-immunoprecipitation, western blotting, flow cytometry with novel Tspan9 antibodies, megakaryocyte SAGE and DNA microarrays The Biochemical journal Medium 18795891
2009 GPVI functions as a receptor for EMMPRIN (CD147/basigin) and mediates platelet rolling on immobilized EMMPRIN under arterial shear. Anti-GPVI blocking antibodies reduce platelet rolling on EMMPRIN-Fc. CHO cells transfected with GPVI show enhanced rolling on EMMPRIN-Fc; CHO cells transfected with EMMPRIN show enhanced rolling on GPVI-Fc. Direct GPVI-EMMPRIN binding was confirmed by ELISA and SPR with KD = 88 nM. Flow-based platelet rolling assay, blocking monoclonal antibodies (anti-EMMPRIN, anti-GPVI), CHO cell transfection, modified ELISA, surface plasmon resonance Thrombosis and haemostasis High 19350111
2009 Lyn, PKC-δ, and SHIP-1 form a complex that specifically regulates GPVI-mediated (but not PAR-mediated) dense granule secretion. GPVI stimulation induces rapid SHIP-1 phosphorylation at Y1020 and association of SHIP-1 and Lyn with PKC-δ. In Lyn-/- platelets, GPVI-mediated phosphorylations of SHIP-1 (Y1020) and PKC-δ (Y311) are inhibited. In Lyn-/- or SHIP-1-/- platelets, GPVI-mediated dense granule secretion is potentiated (negative regulation), while PAR-mediated secretion is inhibited. Lyn-mediated phosphorylation of PKC-δ and SHIP-1 negatively regulates GPVI-specific dense granule secretion. PKC-δ-/-, Lyn-/-, SHIP-1-/- mouse platelets, Co-IP, phosphospecific antibodies, dense granule secretion assays (convulxin vs PAR agonists) Blood High 19587372
2009 The crystal structure of LAIR-1 (a collagen receptor homologous to GPVI's collagen-binding domain) was determined. NMR titrations and mutagenesis mapped the collagen-binding site: residues R59, E61, and W109 are key for collagen interaction. These residues are strictly conserved in both LAIR-1 and GPVI but are located outside the previously proposed GPVI collagen-binding site, revealing an unanticipated common mechanism of collagen recognition. X-ray crystallography (LAIR-1 structure), NMR titrations with collagen peptides, mutagenesis of collagen-contact residues Blood High 20007810
2010 GPVI signals through an ITAM in the associated FcRγ chain via sequential Src family kinase-mediated phosphorylation of the two ITAM tyrosines, followed by Syk SH2 domain binding and activation, culminating in PLCγ2 activation. This mechanistic pathway was established and compared to CLEC-2 signaling (which uses a hemITAM). Review consolidating genetic knockout and biochemical data from multiple studies; mechanistic pathway established by epistasis and phosphorylation cascade analysis Journal of thrombosis and haemostasis Medium 20345705
2011 Cdc42 GTPase is required for GPVI-dependent (CRP-induced) filopodia formation, secretion (ATP and P-selectin), and aggregation in platelets. Cdc42-/- platelets show diminished PAK1/2 phosphorylation (Cdc42 effector) and minimal Akt phosphorylation upon CRP stimulation, establishing Cdc42 as a downstream effector in GPVI signaling. Mx-cre;Cdc42lox/lox inducible knockout mice, CRP and thrombin stimulation, platelet aggregation, P-selectin and ATP release, spreading assay, PAK1/2 phosphorylation, Akt phosphorylation, bleeding time PloS one High 21789221
2013 An adenine insertion (c.711_712insA) in exon 6 of GP6 generates a premature stop codon, producing a truncated GPVI protein (~49 kDa) that lacks the transmembrane domain and is absent from the platelet surface. Platelets from homozygous patients have absent surface GPVI, no aggregation in response to collagen, convulxin, or CRP, and no 14C-5-HT secretion with these agonists, directly establishing that the transmembrane domain is required for functional surface expression. DNA sequencing, mRNA sequencing, western blotting, flow cytometry, immunofluorescence confocal microscopy, platelet aggregation, 14C-5-HT secretion Journal of thrombosis and haemostasis High 23815599
2015 GPVI is a signaling receptor for fibrin. Thrombin-induced fibrin generation activates GPVI-dependent tyrosine phosphorylation of FcRγ and Syk in human and mouse platelets; this is abolished in GPVI-deficient mouse platelets. Mouse platelets spread fully on fibrin (but not fibrinogen) in a GPVI- and Src kinase-dependent manner, associated with phosphatidylserine exposure. The GPVI ectodomain binds directly to immobilized monomeric and polymerized fibrin. GPVI-/- mouse platelets, eptifibatide (αIIbβ3 blocker), PAR4 peptide controls, Syk and FcRγ phosphorylation western blot, platelet spreading on fibrin/fibrinogen, Src kinase inhibitor, SPR-like binding assay Blood High 26282541
2016 GPVI-mediated inhibition of proplatelet formation in megakaryocytes is specifically controlled by collagen type I signaling through receptor-proximal Src family kinases; Syk and LAT are dispensable for this pathway. Integrin α2β1 mediates megakaryocyte binding to collagens. Collagen type IV at the vascular niche may displace collagen I from megakaryocytes, preventing GPVI-mediated inhibition. Megakaryocytes from GPVI-/-, Syk-/-, LAT-/-, and α2β1-/- mice; blocking antibodies; Src family kinase inhibitors; adhesion assays; proplatelet formation assays Journal of cell science High 27505889
2016 TULA-2 protein phosphatase negatively regulates Syk activation downstream of GPVI by dephosphorylating Tyr346, a regulatory (interdomain B) site of Syk that is phosphorylated early after receptor ligation and is critical for initiating full Syk activation. TULA-2 dephosphorylates Tyr346 with high efficiency but is less efficient at other Syk regulatory sites, establishing Tyr346 dephosphorylation as a key checkpoint in GPVI/Syk signaling. In vitro phosphatase assay with recombinant TULA-2 and Syk peptides/protein, phosphospecific antibodies to multiple Syk sites, GPVI-stimulated platelet signaling with TULA-2 loss-of-function The Journal of biological chemistry High 27609517
2017 Pre-existing GPVI dimers on resting platelets coalesce into clusters upon platelet adhesion to collagenous substrates (fibrous collagen I, soluble collagen III, GPVI-specific collagen peptides). GPVI dimer cluster formation depends on a dynamic actin cytoskeleton. Cluster size is substrate-dependent (collagen III most effective). Some GPVI dimer clusters colocalize with areas of phosphotyrosine, indicating signaling activity. This clustering mechanism increases avidity for collagen and facilitates platelet activation. Total internal reflection fluorescence microscopy, direct stochastic optical reconstruction microscopy (dSTORM), confocal microscopy, fluorophore-conjugated GPVI dimer-specific Fab, actin inhibitors Journal of thrombosis and haemostasis High 28058806
2017 Fibrin and D-dimer (but not the E fragment of fibrin) bind to GPVI and activate platelets. D-dimer binds GPVI by SPR with KD of 302 nM for monomeric GPVI. Immobilized D-dimer induces platelet spreading via Src and Syk kinase activation. Fibrin binds selectively to monomeric GPVI (KD 302 nM), in contrast to collagen which binds primarily to dimeric GPVI. Spreading of human platelets on fibrin is abolished in GPVI-deficient patients, confirming fibrin activates human platelets through GPVI. GPVI-deficient human patient platelets, proteolytic fibrin fragments (D-dimer, E fragment), SPR binding assays, platelet spreading on fibrin/D-dimer, Src/Syk inhibitors, soluble D-dimer inhibition assays Blood advances High 29296791
2008 Globular adiponectin (gAd) activates platelets through the GPVI-FcRγ chain complex. gAd stimulates tyrosine phosphorylation of Syk and PLCγ2 (pattern similar to collagen), and this activation is abolished in FcRγ-null platelets (which also lack GPVI). GPVI was confirmed as the receptor for gAd by increased luciferase activity in GPVI-transfected Jurkat T-cells. Full-length adiponectin does not activate platelets through this mechanism. FcRγ-/- and PLCγ2-/- mouse platelets, NFAT luciferase reporter assay in GPVI-transfected Jurkat cells, platelet aggregation, tyrosine phosphorylation western blot Journal of thrombosis and haemostasis High 18419742
2009 PPARγ ligands inhibit GPVI signaling through a non-genomic mechanism. PPARγ associates with Syk and LAT after platelet activation, and PPARγ agonists prevent this association, reducing tyrosine phosphorylation of multiple GPVI signaling components. The inhibitory effect is reversed by the PPARγ antagonist GW9662. Optical aggregometry, spectrofluorimetry (Ca2+ measurement), immunoblot of tyrosine phosphorylation, Co-immunoprecipitation of PPARγ with Syk/LAT, in vitro thrombus formation under flow Journal of thrombosis and haemostasis Medium 20040043
2014 Nox1, but not Nox2, is the key NADPH oxidase regulating GPVI-dependent reactive oxygen species (ROS) production in platelets. Nox1-derived ROS is essential for CRP-dependent thromboxane A2 production via p38 MAPK signaling downstream of GPVI. Neither Nox1 nor Nox2 was significantly involved in CRP-induced platelet aggregation/integrin αIIbβ3 activation, spreading, or granule release. Both Nox1 and Nox2 are involved in collagen-mediated thrombus formation at arterial shear. Nox2-/- mouse platelets, ML171 (Nox1-specific pharmacological inhibitor), H2DCF-DA oxidation assay for ROS, TxA2 ELISA, p38 MAPK inhibitor, ex vivo perfusion Redox biology High 24494191
2014 FAK (focal adhesion kinase) is downstream of Lyn, Syk, PI3K, and Btk, and upstream of Rac1, PLCγ2, Ca2+ release, PKC, Hic-5, Nox1, and αIIbβ3 activation in the GPVI signaling pathway. FAK, but not Pyk2, is essential for GPVI-dependent ROS production, aggregation, phosphatidylserine exposure, P-selectin expression, and integrin αIIbβ3 activation. Pyk2-/- mouse platelets, FAK inhibitor PF-228, Pyk2 inhibitor Tyrphostin A9, CRP stimulation, ROS assay, aggregation, flow cytometry (PS exposure, P-selectin), immunoprecipitation and pulldown for pathway position PloS one Medium 25415317
2014 CEACAM2 negatively regulates GPVI-FcRγ chain signaling in platelets. CEACAM2-/- platelets exhibit enhanced GPVI agonist (CRP, collagen)-induced aggregation, increased adhesion to type I collagen, and hyperresponsive α and dense granule release. In vivo thrombi in Ceacam2-/- mice are larger and more stable than wild-type, establishing CEACAM2 as a novel negative regulator of platelet GPVI-collagen interactions acting through immunoreceptor tyrosine-based inhibitory motifs. Ceacam2-/- mouse platelets, GPVI and CLEC-2 selective agonists, platelet aggregation, granule secretion, adhesion to collagen I, intravital microscopy (FeCl3 and laser injury models) Blood High 25085348
2020 Phosphoproteomics downstream of GPVI/ITAM identified >3000 significant phosphorylation events on >1300 proteins. Key signaling relations were mapped including FcRγ→Syk→PLCγ2→PKCδ→DAPP1. Ras/MAPK axis proteins (KSR1, SOS1, STAT1, Hsp27) and >40 Rab GTPases are regulated downstream of GPVI. GPVI-mediated Rab7 S72 phosphorylation and endolysosomal maturation were blocked by TAK1 inhibition, establishing TAK1 as an upstream regulator of GPVI-induced endolysosomal signaling. Peptide TMT labeling, SPS-MS3 phosphoproteomics, causal inference analysis, TAK1 inhibitor functional validation Blood Medium 32640021
2020 GP6-homozygous platelets (carrying premature stop codon before transmembrane domain) show complete loss of surface GPVI and absence of collagen-induced spreading. Under flow, GP6hom blood fails to form stable platelet aggregates or expose phosphatidylserine (PS) on collagen or noncollagen surfaces (VWF/laminin/rhodocytin), but platelet adhesion is preserved. Thrombin generation is partially reduced. The partial adhesion retention explains the mild bleeding diathesis of GP6hom patients. Western blotting, flow cytometry, platelet spreading on collagen/VWF, whole blood perfusion over collagen or noncollagen surfaces under flow, thrombin generation assay, population frequency analysis Blood advances High 32603422
2021 Dimeric GPVI binds fibrinogen with much higher affinity and slower dissociation rate than monomeric GPVI due to avidity effects. The αC-region of fibrinogen is the primary binding site for GPVI. GPVI interaction with fibrinogen and fibrin (including non-polymerizing fibrin variant) occurs at similar levels, demonstrating GPVI binding is independent of fibrin polymerization. Fibrin polymerization into fibers clusters GPVI through the αC-region, potentially driving downstream signaling. Multiple protein-protein interaction methods (surface-based and solution-based), SPR, competition assays with fibrinogen fragments, non-polymerizing fibrin variant, dimeric vs monomeric GPVI constructs Arteriosclerosis, thrombosis, and vascular biology High 33472402
2021 Crystal structure of monomeric GPVI in complex with nanobody Nb2 revealed: (1) Nb2 binding epitope adjacent to the CRP binding groove in the D1 domain; (2) a novel domain-swapped GPVI dimer conformation via the C-C' loop hinge in D2. Truncation of the C-C' loop hinge prevents domain-swapping and abolishes GPVI signaling in a cell-based NFAT reporter assay without blocking ligand binding, establishing that the C-C' loop/domain-swapped structure is required for GPVI signaling but not ligand binding. X-ray crystallography of GPVI-Nb2 complex, C-C' loop truncation mutagenesis, NFAT luciferase reporter assay, Nb2 collagen/CRP displacement binding assay Blood High 33512486
2021 Both CLEC-2 and GPVI (via FcRγ chain) are platelet hemin receptors. Hemin directly binds to both CLEC-2 and GPVI as shown by western blotting and SPR, activating platelets by stimulating SYK and PLCγ2 phosphorylation. Hemin-induced murine platelet aggregation is partially reduced in CLEC-2-depleted or FcRγ-deficient platelets and almost completely inhibited in CLEC-2-depleted FcRγ-deficient double-knockout platelets. SPR binding of hemin to CLEC-2 and GPVI, western blotting, CLEC-2-depleted and FcRγ-/- mouse platelets, double-knockout model, GPVI antibody JAQ-1 inhibition, platelet aggregation Blood advances High 33843987
2022 Anti-GPVI nanobody Nb2 blocks GPVI-mediated signaling (Syk, LAT, PLCγ2 phosphorylation) and thrombus formation on collagen and atherosclerotic plaque. Non-blocking Nb28 reveals GPVI forms distinct distribution patterns on collagen (clusters along fibers) vs. plaque; clustering on collagen fibers is abolished by Nb2. GPVI clustering is required for downstream signaling and thrombus formation. Adhesion to plaque is maintained despite GPVI signaling blockade and is not inhibited by α2β1 alone. Anti-GPVI nanobodies, western blot of Syk/LAT/PLCγ2 phosphorylation, whole blood thrombus formation under flow, super-resolution/fluorescence microscopy with labeled Nb28, integrin blocking antibodies Journal of thrombosis and haemostasis High 35894121
2023 GPVI plays a key role in neutrophil recruitment, platelet-neutrophil complex (PNC) formation, and NETosis during acute lung injury (ALI). Anti-GPVI treatment results in less stable platelet-neutrophil interactions, reduced neutrophil crawling and adhesion on endothelial cells, reduced neutrophil transmigration and alveolar infiltrates, and strongly reduced NET formation. GPVI-deficient mice are markedly protected from pulmonary inflammation in LPS-induced ALI, without increased pulmonary bleeding. GPVI-deficient mice, anti-GPVI antibody treatment, LPS-induced ALI model, intravital confocal microscopy of ventilated lung, high-resolution multicolor microscopy of lung sections, PNC quantification, NET staining Blood High 37441848
2003 PLCγ1 partially compensates for PLCγ2 downstream of GPVI in mouse (but not human) platelets. CRP and collagen stimulate tyrosine phosphorylation of PLCγ1 at Tyr783 in mouse platelets through a Src kinase-dependent pathway. In PLCγ2-/- platelets, weak collagen-induced integrin activation persists via PLCγ1 and PI3-kinase signaling downstream of GPVI. Adhesion of PLCγ2-/- platelets to collagen under shear is severely reduced but not abolished (unlike FcRγ-/- platelets). PLCγ2-/- and FcRγ-/- mouse platelets, PLCγ1 phosphospecific antibody (pTyr783), PP1 (Src inhibitor), wortmannin (PI3K inhibitor), αIIbβ3 and α2β1 inhibitors, Born aggregometry, collagen adhesion under flow Blood High 12730118

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1995 The use of general primers GP5 and GP6 elongated at their 3' ends with adjacent highly conserved sequences improves human papillomavirus detection by PCR. The Journal of general virology 1073 9049358
2003 Platelet-collagen interaction: is GPVI the central receptor? Blood 880 12649139
1997 A general primer GP5+/GP6(+)-mediated PCR-enzyme immunoassay method for rapid detection of 14 high-risk and 6 low-risk human papillomavirus genotypes in cervical scrapings. Journal of clinical microbiology 484 9041439
1997 PCR detection of human papillomavirus: comparison between MY09/MY11 and GP5+/GP6+ primer systems. Journal of clinical microbiology 378 9163434
2005 GPVI and integrin alphaIIb beta3 signaling in platelets. Journal of thrombosis and haemostasis : JTH 323 16102042
1997 Platelet activation and signal transduction by convulxin, a C-type lectin from Crotalus durissus terrificus (tropical rattlesnake) venom via the p62/GPVI collagen receptor. The Journal of biological chemistry 299 9153205
2019 Functional significance of the platelet immune receptors GPVI and CLEC-2. The Journal of clinical investigation 251 30601137
2007 Controlled shedding of platelet glycoprotein (GP)VI and GPIb-IX-V by ADAM family metalloproteinases. Journal of thrombosis and haemostasis : JTH 218 17445093
2015 Fibrin activates GPVI in human and mouse platelets. Blood 178 26282541
2008 Homogeneous amplification of genital human alpha papillomaviruses by PCR using novel broad-spectrum GP5+ and GP6+ primers. Journal of clinical microbiology 161 18199790
1999 LAT is required for tyrosine phosphorylation of phospholipase cgamma2 and platelet activation by the collagen receptor GPVI. Molecular and cellular biology 153 10567557
2010 GPVI and CLEC-2 in hemostasis and vascular integrity. Journal of thrombosis and haemostasis : JTH 150 20345705
2002 Analysis of the interaction of platelet collagen receptor glycoprotein VI (GPVI) with collagen. A dimeric form of GPVI, but not the monomeric form, shows affinity to fibrous collagen. The Journal of biological chemistry 139 12356768
2003 Tec regulates platelet activation by GPVI in the absence of Btk. Blood 136 12842985
2005 Laminin stimulates spreading of platelets through integrin alpha6beta1-dependent activation of GPVI. Blood 135 16219796
2005 GPVI and alpha2beta1 play independent critical roles during platelet adhesion and aggregate formation to collagen under flow. Blood 130 15886326
2001 The platelet receptor GPVI mediates both adhesion and signaling responses to collagen in a receptor density-dependent fashion. The Journal of biological chemistry 130 11723134
2006 Thrombin overcomes the thrombosis defect associated with platelet GPVI/FcRgamma deficiency. Blood 127 16391010
2012 Platelet GPVI: a target for antithrombotic therapy?! Trends in pharmacological sciences 118 22901552
2010 Differentially regulated GPVI ectodomain shedding by multiple platelet-expressed proteinases. Blood 105 20644114
2003 GPVI levels in platelets: relationship to platelet function at high shear. Blood 102 12829582
2014 The role of Nox1 and Nox2 in GPVI-dependent platelet activation and thrombus formation. Redox biology 99 24494191
2019 Safety and Tolerability, Pharmacokinetics, and Pharmacodynamics of ACT017, an Antiplatelet GPVI (Glycoprotein VI) Fab. Arteriosclerosis, thrombosis, and vascular biology 98 31017822
2017 Clustering of glycoprotein VI (GPVI) dimers upon adhesion to collagen as a mechanism to regulate GPVI signaling in platelets. Journal of thrombosis and haemostasis : JTH 90 28058806
2004 Differential regulation of actin stress fiber assembly and proplatelet formation by alpha2beta1 integrin and GPVI in human megakaryocytes. Blood 86 15265786
2003 Murine GPVI stimulates weak integrin activation in PLCgamma2-/- platelets: involvement of PLCgamma1 and PI3-kinase. Blood 85 12730118
2023 A key role for platelet GPVI in neutrophil recruitment, migration, and NETosis in the early stages of acute lung injury. Blood 78 37441848
2004 GPVI down-regulation in murine platelets through metalloproteinase-dependent shedding. Thrombosis and haemostasis 77 15116256
2004 Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI antibodies in mice. Blood 74 15507524
2013 The GPVI-Fc fusion protein Revacept improves cerebral infarct volume and functional outcome in stroke. PloS one 73 23935828
2020 Phosphoproteomic quantitation and causal analysis reveal pathways in GPVI/ITAM-mediated platelet activation programs. Blood 72 32640021
2002 Differential requirement for LAT and SLP-76 in GPVI versus T cell receptor signaling. The Journal of experimental medicine 72 11901197
2009 EMMPRIN (CD147) is a novel receptor for platelet GPVI and mediates platelet rolling via GPVI-EMMPRIN interaction. Thrombosis and haemostasis 71 19350111
2012 The dimeric platelet collagen receptor GPVI-Fc reduces platelet adhesion to activated endothelium and preserves myocardial function after transient ischemia in mice. American journal of physiology. Cell physiology 69 22814400
2017 Fibrin and D-dimer bind to monomeric GPVI. Blood advances 67 29296791
2009 The crystal structure of bacteriophage HK97 gp6: defining a large family of head-tail connector proteins. Journal of molecular biology 67 19895817
2005 Touchdown General Primer (GP5+/GP6+) PCR and optimized sample DNA concentration support the sensitive detection of human papillomavirus. BMC clinical pathology 67 16288661
2016 Inhibition of Platelet GPVI Protects Against Myocardial Ischemia-Reperfusion Injury. Arteriosclerosis, thrombosis, and vascular biology 66 26916731
2015 Oral administration of Bruton's tyrosine kinase inhibitors impairs GPVI-mediated platelet function. American journal of physiology. Cell physiology 63 26659727
2013 An adenine insertion in exon 6 of human GP6 generates a truncated protein associated with a bleeding disorder in four Chilean families. Journal of thrombosis and haemostasis : JTH 63 23815599
2012 The bispecific SDF1-GPVI fusion protein preserves myocardial function after transient ischemia in mice. Circulation 63 22223428
2001 Expression of the platelet receptor GPVI confers signaling via the Fc receptor gamma -chain in response to the snake venom convulxin but not to collagen. The Journal of biological chemistry 63 11152687
2007 Mapping the platelet profile for functional genomic studies and demonstration of the effect size of the GP6 locus. Journal of thrombosis and haemostasis : JTH 62 17663743
2009 Identification of Tspan9 as a novel platelet tetraspanin and the collagen receptor GPVI as a component of tetraspanin microdomains. The Biochemical journal 61 18795891
2021 Platelet GPVI (Glycoprotein VI) and Thrombotic Complications in the Venous System. Arteriosclerosis, thrombosis, and vascular biology 60 34496636
2009 Crystal structure and collagen-binding site of immune inhibitory receptor LAIR-1: unexpected implications for collagen binding by platelet receptor GPVI. Blood 60 20007810
2006 Comparison between the Hybrid Capture II Test and an SPF1/GP6+ PCR-based assay for detection of human papillomavirus DNA in cervical swab samples. Journal of clinical microbiology 59 16672400
2007 Diverging signaling events control the pathway of GPVI down-regulation in vivo. Blood 58 17374738
2013 The GPVI-Fc fusion protein Revacept reduces thrombus formation and improves vascular dysfunction in atherosclerosis without any impact on bleeding times. PloS one 56 23951109
2009 Molecular priming of Lyn by GPVI enables an immune receptor to adopt a hemostatic role. Proceedings of the National Academy of Sciences of the United States of America 55 19940238
2009 Non-genomic effects of PPARgamma ligands: inhibition of GPVI-stimulated platelet activation. Journal of thrombosis and haemostasis : JTH 55 20040043
2005 Rapid ubiquitination of Syk following GPVI activation in platelets. Blood 54 15701717
2001 A novel viper venom metalloproteinase, alborhagin, is an agonist at the platelet collagen receptor GPVI. The Journal of biological chemistry 54 11344165
2016 GPVI and Thromboxane Receptor on Platelets Promote Proinflammatory Macrophage Phenotypes during Cutaneous Inflammation. The Journal of investigative dermatology 52 27818280
2009 Lyn, PKC-delta, SHIP-1 interactions regulate GPVI-mediated platelet-dense granule secretion. Blood 52 19587372
2011 Gene targeting implicates Cdc42 GTPase in GPVI and non-GPVI mediated platelet filopodia formation, secretion and aggregation. PloS one 50 21789221
2014 Targeting GPVI as a novel antithrombotic strategy. Journal of blood medicine 48 24899824
2012 The roles of SaPI1 proteins gp7 (CpmA) and gp6 (CpmB) in capsid size determination and helper phage interference. Virology 48 22709958
2018 Soluble GPVI is elevated in injured patients: shedding is mediated by fibrin activation of GPVI. Blood advances 46 29437639
2009 Regulation of platelet glycoprotein VI (GPVI) surface expression and of soluble GPVI in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS). Basic research in cardiology 46 19190951
2003 Activation of GPVI by collagen is regulated by alpha2beta1 and secondary mediators. Journal of thrombosis and haemostasis : JTH 45 12871331
2020 Loss of GPVI and GPIbα contributes to trauma-induced platelet dysfunction in severely injured patients. Blood advances 44 32556282
2021 Heme activates platelets and exacerbates rhabdomyolysis-induced acute kidney injury via CLEC-2 and GPVI/FcRγ. Blood advances 43 33843987
2001 Expression and function of the collagen receptor GPVI during megakaryocyte maturation. The Journal of biological chemistry 42 11278467
2018 GPVI surface expression and signalling pathway activation are increased in platelets from obese patients: Elucidating potential anti-atherothrombotic targets in obesity. Atherosclerosis 41 30658193
2009 Influence of platelet count on the expression of platelet collagen receptor glycoprotein VI (GPVI) in patients with acute coronary syndrome. Thrombosis and haemostasis 41 19404545
2020 Novel antiplatelet strategies targeting GPVI, CLEC-2 and tyrosine kinases. Platelets 40 33307909
2015 Differential Inhibition of Human Atherosclerotic Plaque-Induced Platelet Activation by Dimeric GPVI-Fc and Anti-GPVI Antibodies: Functional and Imaging Studies. Journal of the American College of Cardiology 40 26046734
2020 Flow studies on human GPVI-deficient blood under coagulating and noncoagulating conditions. Blood advances 39 32603422
2016 Proplatelet formation is selectively inhibited by collagen type I through Syk-independent GPVI signaling. Journal of cell science 39 27505889
2014 Preserved bioactivity and tunable release of a SDF1-GPVI bi-specific protein using photo-crosslinked PEGda hydrogels. Biomaterials 38 24875761
2000 Roles of SLP-76, phosphoinositide 3-kinase, and gelsolin in the platelet shape changes initiated by the collagen receptor GPVI/FcR gamma-chain complex. Blood 38 11090061
2011 GPVI and GPIbα mediate staphylococcal superantigen-like protein 5 (SSL5) induced platelet activation and direct toward glycans as potential inhibitors. PloS one 37 21552524
2009 Anti-glycoprotein VI monoclonal antibodies directly aggregate platelets independently of FcgammaRIIa and induce GPVI ectodomain shedding. Platelets 37 19235048
2018 Significant Hypo-Responsiveness to GPVI and CLEC-2 Agonists in Pre-Term and Full-Term Neonatal Platelets and following Immune Thrombocytopenia. Thrombosis and haemostasis 36 29695020
2015 Activation of glycoprotein VI (GPVI) and C-type lectin-like receptor-2 (CLEC-2) underlies platelet activation by diesel exhaust particles and other charged/hydrophobic ligands. The Biochemical journal 35 25849538
2013 Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway. PloS one 34 24386454
2009 Novel interactions in platelet biology: CLEC-2/podoplanin and laminin/GPVI. Journal of thrombosis and haemostasis : JTH 34 19630798
2006 Definition of novel GP6 polymorphisms and major difference in haplotype frequencies between populations by a combination of in-depth exon resequencing and genotyping with tag single nucleotide polymorphisms. Journal of thrombosis and haemostasis : JTH 33 16706959
2003 Collagen platelet receptor polymorphisms integrin alpha2beta1 C807T and GPVI Q317L and risk of ischemic stroke. Journal of thrombosis and haemostasis : JTH 33 12871362
2021 Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function. American journal of physiology. Cell physiology 32 33689480
2010 Phenotypic approaches to gene mapping in platelet function disorders - identification of new variant of P2Y12, TxA2 and GPVI receptors. Hamostaseologie 32 20162250
2008 Globular adiponectin induces platelet activation through the collagen receptor GPVI-Fc receptor gamma chain complex. Journal of thrombosis and haemostasis : JTH 32 18419742
2021 GPVI (Glycoprotein VI) Interaction With Fibrinogen Is Mediated by Avidity and the Fibrinogen αC-Region. Arteriosclerosis, thrombosis, and vascular biology 31 33472402
2018 Does fibrin(ogen) bind to monomeric or dimeric GPVI, or not at all? Platelets 30 30110193
2018 Human Platelet Protein Ubiquitylation and Changes following GPVI Activation. Thrombosis and haemostasis 29 30597505
2022 GPVI expression is linked to platelet size, age, and reactivity. Blood advances 28 35561312
2016 TULA-2 Protein Phosphatase Suppresses Activation of Syk through the GPVI Platelet Receptor for Collagen by Dephosphorylating Tyr(P)346, a Regulatory Site of Syk. The Journal of biological chemistry 28 27609517
2014 CEACAM2 negatively regulates hemi (ITAM-bearing) GPVI and CLEC-2 pathways and thrombus growth in vitro and in vivo. Blood 28 25085348
2014 α2β1 integrin, GPVI receptor, and common FcRγ chain on mouse platelets mediate distinct responses to collagen in models of thrombosis. PloS one 28 25415203
2008 Differential roles for the adapters Gads and LAT in platelet activation by GPVI and CLEC-2. Journal of thrombosis and haemostasis : JTH 28 18826392
2021 Acquired platelet GPVI receptor dysfunction in critically ill patients with sepsis. Blood 27 33827131
2019 miR-15a-5p regulates expression of multiple proteins in the megakaryocyte GPVI signaling pathway. Journal of thrombosis and haemostasis : JTH 27 30632265
2019 Targeting Platelet GPVI Plus rt-PA Administration but Not α2β1-Mediated Collagen Binding Protects against Ischemic Brain Damage in Mice. International journal of molecular sciences 27 31022936
2014 Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation. PloS one 27 25415317
2007 The Modifier of hemostasis (Mh) locus on chromosome 4 controls in vivo hemostasis of Gp6-/- mice. Blood 27 17991808
2006 GPVI potentiation of platelet activation by thrombin and adhesion molecules independent of Src kinases and Syk. Arteriosclerosis, thrombosis, and vascular biology 27 17110603
2005 Thrombopoietin initiates demethylation-based transcription of GP6 during megakaryocyte differentiation. Blood 27 15701720
2022 Anti-GPVI nanobody blocks collagen- and atherosclerotic plaque-induced GPVI clustering, signaling, and thrombus formation. Journal of thrombosis and haemostasis : JTH 26 35894121
2021 Structural characterization of a novel GPVI-nanobody complex reveals a biologically active domain-swapped GPVI dimer. Blood 26 33512486

Missed literature

Know a paper Affinage missed for GP6? Flag it for the maintainers and the community.

No submissions yet.