Affinage

ITGA2B

Integrin alpha-IIb · UniProt P08514

Length
1039 aa
Mass
113.4 kDa
Annotated
2026-06-10
100 papers in source corpus 24 papers cited in narrative 24 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

ITGA2B (αIIb/GPIIb) is the platelet-specific α subunit that pairs obligately with β3 (GPIIIa) to form the αIIbβ3 (GPIIb-IIIa) integrin, the principal receptor mediating fibrinogen binding and platelet aggregation induced by physiologic agonists (PMID:8578476). The subunit is synthesized in megakaryocytes as a glycosylated precursor whose assembly with β3 is an obligatory checkpoint for heterodimer maturation and surface expression; unassembled β3 is retained intracellularly, and co-expression of β3 rescues maturation of αIIb (PMID:3108266, PMID:2477081). The transmembrane and cytoplasmic domains of αIIb — but not those of β3 — are required for surface trafficking of the complex, a requirement underscored by a disease truncation (Ser870→stop) that permits heterodimer association yet abolishes maturation and surface display (PMID:1540596, PMID:8904900). On the platelet surface the receptor is held in a low-affinity state and switches to a fibrinogen-competent conformation through inside-out signaling; convergent G-protein routes (Gq+Gi versus Gi+Gz) drive this activation, with the Gi+Gz pathway requiring Src-family kinases and the Gq+Gi pathway being calcium-dependent (PMID:15546949), and upstream transcription-factor programs (RUNX1/CBFA2-PKCθ) feed into this inside-out cascade (PMID:14525764). Beyond ligand capture, αIIb-dependent outside-in signaling through Gα13 and a c-Src/14-3-3ζ axis organizes lamellipodium formation and directional platelet migration (PMID:37018659), and the engaged receptor couples to actomyosin-driven cytoskeletal rearrangement required for filopodium formation and aggregation (PMID:2207330). A gain-of-function mutation (R995W) constitutively activates the receptor, producing spontaneous ligand binding and FAK phosphorylation and causing macrothrombocytopenia through defective proplatelet formation (PMID:21454453). Transcription of the gene is restricted to the megakaryocytic lineage by promoter elements bound combinatorially by GATA, Ets, and Sp1 factors and by ERK-induced MafB, and the locus is epigenetically gated by H3K27me3/Jmjd3 during hematopoietic commitment (PMID:2026605, PMID:15121870, PMID:22952660). The receptor also participates in pathological thrombosis (e.g., CLEC-2–cooperative cerebral venous sinus thrombosis) and serves as a validated antithrombotic drug target (PMID:8578476, PMID:39195988).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1987 High

    Established how αIIb is produced and processed in its native cell, defining the biosynthetic substrate from which the mature receptor is built.

    Evidence Pulse-chase metabolic labeling with glycosidase/inhibitor treatment in primary human megakaryocytes

    PMID:3108266

    Open questions at the time
    • Did not address how assembly with β3 controls processing
    • No structural detail of the precursor
  2. 1989 High

    Showed that αIIb-β3 assembly is the obligatory gate for heterodimer maturation and surface expression, explaining why neither subunit reaches the surface alone.

    Evidence Pulse-chase, reciprocal immunoprecipitation, and β3 co-expression rescue in megakaryocytes and the LAMA-84 cell line

    PMID:2477081

    Open questions at the time
    • Did not map which domains mediate the assembly requirement
    • ER retention machinery for unassembled subunits not identified
  3. 1990 Medium

    Determined the full-length αIIb (and β3) coding sequence, providing the molecular framework for mutagenesis and disease-variant analysis.

    Evidence cDNA library construction and sequencing from human megakaryocytes

    PMID:2345548

    Open questions at the time
    • Single-lab sequence; cell-type sequence differences not functionally validated
    • No structure-function annotation
  4. 1991 High

    Localized the megakaryocyte-specific transcriptional control to defined 5'-flanking elements, beginning the explanation of why the gene is lineage-restricted.

    Evidence CAT reporter deletions, DNase I footprinting, and EMSA in megakaryocytic vs non-megakaryocytic cells

    PMID:2026605

    Open questions at the time
    • Identity of the megakaryocyte-specific binding factors not determined here
    • Did not link promoter activity to differentiation signals
  5. 1991 Medium

    Demonstrated that a conformational change in the heterodimer alone can expose the fibrinogen receptor, dissociating receptor activation from canonical intracellular signaling.

    Evidence Antibody (D3GP3)-induced aggregation with Ca2+, phosphorylation, G-protein, and pharmacologic controls

    PMID:1957276

    Open questions at the time
    • Structural basis of the conformational switch not resolved
    • Single-lab antibody-based perturbation
  6. 1991 High

    Clarified that some anti-CD41 antibodies activate platelets indirectly via FcgammaRII crosslinking rather than through direct receptor signaling, distinguishing artefactual from intrinsic activation.

    Evidence F(ab')2 fragments, anti-FcgammaRII blockade, cell-mixing and viscosity experiments

    PMID:1832937

    Open questions at the time
    • Does not address physiologic inside-out activation
    • Mechanism specific to IgG immune complexes
  7. 1992 High

    Mapped the trafficking determinant to the αIIb transmembrane/cytoplasmic region, showing β3's cytoplasmic tail is dispensable for surface expression.

    Evidence COS-cell transfection with TM/cytoplasmic deletion mutants, Co-IP, and immunofluorescence

    PMID:1540596

    Open questions at the time
    • Did not identify the trafficking machinery engaging the αIIb tail
    • Lower-efficiency extracellular dimerization not mechanistically explained
  8. 1995 High

    Cemented αIIbβ3 as the universal fibrinogen receptor for platelet aggregation and validated it as an antithrombotic target across inhibitor classes.

    Evidence In vitro aggregation, animal thrombosis models, and a Phase III clinical trial with abciximab and RGD-based inhibitors

    PMID:8578476

    Open questions at the time
    • Did not dissect upstream activation pathways
    • Outside-in signaling roles not addressed
  9. 1990 Medium

    Linked receptor engagement to actomyosin-driven cytoskeletal remodeling, revealing a signaling role beyond passive ligand binding.

    Evidence EM, immunolabel-surface replication, and cytoskeletal/aggregation assays with anti-GPIIb/anti-GPIIIa antibodies

    PMID:2207330

    Open questions at the time
    • Molecular link between receptor and cytoskeleton not defined
    • Antibody-clamping artifact not fully excluded
  10. 1995 Medium

    Showed receptor-specific spatial sorting during spreading, with αIIbβ3 internalizing into the open canalicular system distinct from GPIb/IX redistribution.

    Evidence Gold-labeled ligand tracking by electron microscopy during platelet spreading

    PMID:7647005

    Open questions at the time
    • Functional consequence of OCS sequestration unresolved
    • Trafficking mechanism not identified
  11. 2003 Medium

    Connected the RUNX1/CBFA2 transcriptional program to inside-out activation competence via PKC-theta and pleckstrin phosphorylation.

    Evidence Patient platelet analysis with immunoblotting, PAC-1 flow cytometry, and aggregation assays

    PMID:14525764

    Open questions at the time
    • Single-patient observation
    • Direct RUNX1 targets controlling activation not fully enumerated
  12. 2004 High

    Resolved two divergent G-protein routes to inside-out activation, distinguishing a calcium-dependent Gq+Gi pathway from a Src-kinase-dependent Gi+Gz pathway.

    Evidence Aggregometry, PAC-1 binding, calcium chelation, PP2 inhibition, and knockout-mouse platelets

    PMID:15546949

    Open questions at the time
    • Convergence point on the integrin tail not identified
    • Relative physiologic weighting of pathways unresolved
  13. 2004 High

    Defined the proximal promoter logic, showing GATA/Ets/Sp1 and ERK-induced MafB act combinatorially to drive megakaryocytic CD41 transcription.

    Evidence Promoter-reporter mutagenesis and dominant-negative/antisense MafB in differentiation assays

    PMID:15121870

    Open questions at the time
    • Endogenous chromatin context not addressed here
    • Upstream ERK activators not specified
  14. 2005 Medium

    Extended the receptor's repertoire to non-canonical ligands and cell contexts, identifying ADAM15 as an activation-dependent adhesion ligand and documenting CD41 roles in mast cells.

    Evidence Adhesion assays with blocking antibodies and activation-marker flow cytometry; gpIIb-/- mast cell adhesion studies

    PMID:15781330 PMID:16268472

    Open questions at the time
    • Physiologic relevance of ADAM15 engagement in vivo unclear
    • Mast cell adhesion phenotype is compensatory and indirect
  15. 2006 High

    Showed bacterial pathogens exploit the low-affinity receptor through fibrinogen/fibronectin bridges plus FcgammaRIIa, mechanistically linking αIIbβ3 to infective platelet activation.

    Evidence Aggregation assays with FnBPA truncation constructs in heterologous bacteria and receptor-blocking antibodies

    PMID:16359330

    Open questions at the time
    • In vivo contribution to endocarditis not tested here
    • Does not address direct receptor conformation change
  16. 2007 Medium

    Demonstrated horizontal transfer of functional αIIbβ3 to neutrophils, where it cooperates with β2-integrins to drive NF-kappaB signaling, broadening the receptor's inflammatory role.

    Evidence Confocal co-localization, NF-kappaB Western/EMSA, RT-PCR, and Src/Syk inhibitors in PMP-loaded neutrophils

    PMID:17644514

    Open questions at the time
    • Single-lab observation
    • In vivo significance of transferred receptor unestablished
  17. 2011 High

    Identified R995W as a constitutively activating mutation causing macrothrombocytopenia via defective proplatelet formation, mechanistically tying receptor activation state to thrombopoiesis.

    Evidence PAC-1/fibrinogen binding, FAK phosphorylation, cell-morphology assays, and proplatelet assays in transfected cells and fetal-liver megakaryocytes, confirmed in 4 families

    PMID:21454453

    Open questions at the time
    • Precise structural mechanism of constitutive activation not detailed
    • Link between activation and proplatelet defect mechanistically incomplete
  18. 2012 Medium

    Added an epigenetic layer to lineage restriction, showing H3K27me3/Jmjd3 dynamics gate Itga2b expression during megakaryocytic commitment.

    Evidence ChIP for histone marks and RT-PCR for Jmjd3/Itga2b across hematopoietic cell types

    PMID:22952660

    Open questions at the time
    • Correlative without direct Jmjd3 knockout at the locus
    • Internal promoter mechanism not fully resolved
  19. 2020 Medium

    Implicated CD41 in exosome-borne CD41–β3–FAK–Akt–Runx2 signaling supporting MSC osteogenesis, indicating a role outside hemostasis.

    Evidence Exosome proteomics, CD41 siRNA, FAK/Akt/Runx2 immunoblotting, and differentiation/migration assays with a rat ONFH model

    PMID:32341357

    Open questions at the time
    • Single-lab study
    • How exosomal CD41 engages target-cell β3 not defined
  20. 2022 High

    Established αIIbβ3 as a driver and therapeutic target in pathological thrombosis, with receptor blockade rescuing CLEC-2-cooperative cerebral venous sinus thrombosis.

    Evidence Antibody-induced mouse CVT model with intravital imaging, pharmacologic GPIIb/IIIa and CLEC-2 blockade, and therapeutic rescue

    PMID:39195988

    Open questions at the time
    • Molecular cooperation between CLEC-2 and αIIbβ3 signaling not fully mapped
    • Translation to human CVT therapy untested here
  21. 2023 High

    Defined an outside-in migration program in which αIIbβ3 couples to Gα13 and a c-Src/14-3-3ζ axis to polarize platelets, distinguishing migration from classical aggregation.

    Evidence Morphodynamic profiling, selective inhibitors (dasatinib), 4D intravital microscopy, patient platelets, and actin/myosin perturbation

    PMID:37018659

    Open questions at the time
    • Structural basis of Gα13 coupling to αIIb tail unresolved
    • Physiologic triggers of the polarization program not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How inside-out and outside-in signals are integrated at the αIIb cytoplasmic tail at the structural level, and how the same receptor switches between aggregation, migration, and pathological consumption programs, remains unresolved.
  • No structural model of the activated cytoplasmic tail signaling complex in the corpus
  • Mechanistic determinants choosing migration vs aggregation outputs unknown
  • Integration of transcriptional/epigenetic control with receptor signaling not unified

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0098631 cell adhesion mediator activity 3 GO:0038024 cargo receptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005856 cytoskeleton 2
Pathway
R-HSA-109582 Hemostasis 3 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 3
Partners
ADAM15FGAITGB3SRCYWHAZ
Complex memberships
αIIbβ3 (GPIIb-IIIa) integrin

Evidence

Reading pass · 24 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1987 GPIIb is synthesized in megakaryocytes as a precursor of Mr 130,000 containing both alpha and beta subunits; this precursor is processed with a half-life of 4–5 h, converting high-mannose oligosaccharides to complex-type carbohydrates to yield mature GPIIb alpha (116 kDa) and GPIIb beta (25 kDa) subunits. GPIIIa polypeptide backbone is 90 kDa with no detectable post-translational processing of the chain. Pulse-chase metabolic labeling with [35S]methionine, immunoprecipitation with subunit-specific antibodies, tunicamycin/monensin treatment, endoglycosidase H digestion of purified human megakaryocytes The Journal of cell biology High 3108266
1989 Assembly of pro-GPIIb with GPIIIa is an obligatory step for maturation of the GPIIb-IIIa heterodimer and its surface expression. A large pool (~60%) of unassociated GPIIIa exists and is not surface-exposed; GPIIb and pro-GPIIb molecules are nearly all found associated with GPIIIa. Expression of GPIIIa in a megakaryocytic cell line that only produces pro-GPIIb (and cannot process it) rescues mature GPIIb production and surface expression of the complex. Pulse-chase experiments, immunoprecipitation with subunit-specific antibodies on human megakaryocytes and the LAMA-84 megakaryocytic cell line, co-transfection rescue experiments Blood High 2477081
1990 Full-length cDNA sequences for GPIIb and GPIIIa were determined from human megakaryocyte cDNA libraries, revealing a nucleotide difference at position 633 of GPIIb (cysteine in megakaryocyte vs. serine in HEL cells) and differences in GPIIIa sequence compared to endothelial cell-derived cDNA. cDNA library construction from human megakaryocytes, cDNA sequencing Molecular biology reports Medium 2345548
1991 The 5'-flanking region of the GPIIb gene (from -643 to +33) drives megakaryocyte-specific transcription. Two domains at positions -460 and -510 interact exclusively with proteins present in megakaryocytic cells and act as positive transcription factor binding sites; deletion of this region significantly decreases promoter activity. Other domains (at -54, -233, -345, -540) bind more broadly expressed nuclear factors. CAT reporter transfection in megakaryocytic and non-megakaryocytic cells, DNase I footprinting, gel mobility shift assays The Journal of biological chemistry High 2026605
1992 The transmembrane and cytoplasmic domains of the GPIIb (alphaIIb) subunit are necessary for surface expression of the GPIIb-IIIa complex, whereas the corresponding domains of GPIIIa (beta3) are not required. The extracellular domains of both subunits can form a heterodimer in the absence of transmembrane/cytoplasmic domains, albeit with lower efficiency. COS cell transfection with full-length and deletion mutant cDNAs (GPIIb delta1 lacking TM/cytoplasmic domain; GPIIIa delta-m lacking TM/cytoplasmic domain), immunoprecipitation, immunofluorescence Biochemistry High 1540596
1991 Binding of the anti-GPIIIa monoclonal antibody D3GP3 to GPIIIa within intact GPIIb-IIIa complexes induces fibrinogen binding and platelet aggregation without triggering Ca2+ mobilization, protein phosphorylation, or pertussis toxin-sensitive G-protein activation, and the aggregation is not blocked by PGE1, aspirin, or apyrase. This demonstrates that a conformational change in GPIIb-IIIa can expose the fibrinogen receptor in an activation-independent fashion. Platelet aggregometry, Ca2+ mobilization assay, protein phosphorylation analysis, pertussis toxin treatment, pharmacologic inhibitor panel, scanning electron microscopy Thrombosis research Medium 1957276
1991 Anti-CD41 IgG antibody (UR1) activates platelets via an Fc receptor-dependent cell-cell interaction mechanism: UR1 binds CD41 on one platelet forming immune complexes that then crosslink and stimulate FcgammaRII on adjacent platelets. F(ab')2 fragments of UR1 fail to activate platelets and inhibit IgG-mediated activation; anti-FcgammaRII antibody blocks activation; high-viscosity media that impede cell-cell contact inhibit activation. Platelet aggregometry, Ca2+ mobilization assay, F(ab')2 fragment generation, anti-FcgammaRII blocking antibody, high-viscosity inhibition, cell-mixing experiments British journal of haematology High 1832937
1995 GPIIb-IIIa (alphaIIbbeta3) is the platelet receptor for fibrinogen and mediates platelet aggregation induced by all physiologic agonists; blockade with the Fab fragment of chimeric monoclonal antibody 7E3 (abciximab), RGD-containing snake venom peptides, or RGD-based peptidomimetics abolishes platelet aggregation and platelet thrombus formation. In vitro platelet aggregation assay, in vivo animal thrombosis models, EPIC Phase III clinical trial Thrombosis and haemostasis High 8578476
1996 A homozygous nonsense mutation (Ser870→stop) in the GPIIb heavy chain truncates GPIIb by 138 amino acids, removing the transmembrane and intracytoplasmic domains. The truncated GPIIb can associate with GPIIIa, but the heterodimer fails to mature (as shown by endoglycosidase H sensitivity) and is not expressed on the cell surface, establishing that the GPIIb light chain region is required for maturation and surface trafficking. Cotransfection of mutant GPIIb and wild-type GPIIIa in COS-7 cells, immunoprecipitation, endoglycosidase H digestion, flow cytometry British journal of haematology High 8904900
2004 ERK signaling promotes megakaryocyte differentiation by driving transcription from the proximal GPIIb (CD41) promoter (within 114 bp upstream of the TSS). GATA, Ets, and Sp1 consensus sequences within this region each function combinatorially and are each necessary for ERK-activated transcription. ERK induces MafB/Kreisler, which synergizes with GATA and Ets factors to enhance GPIIb promoter activity; dominant-negative or antisense suppression of MafB inhibits ERK-dependent transactivation. Promoter-reporter transfection assays, site-directed mutagenesis of GATA/Ets/Sp1 sites, dominant-negative and antisense MafB constructs, megakaryocyte differentiation assays Molecular and cellular biology High 15121870
2004 Combined G(i) and G(z) signaling pathways activate platelet GPIIb/IIIa and cause platelet aggregation through a mechanism that requires Src family tyrosine kinases but shows only a minor calcium requirement, distinct from the G(q)+G(i) pathway which is dependent on intracellular calcium but insensitive to Src family kinase inhibitors. Src family kinase inhibitor PP2 inhibits PAC-1 binding (GPIIb/IIIa activation) and thromboxane generation downstream of G(i)+G(z) but not G(q)+G(i). Platelet aggregometry, PAC-1 binding by flow cytometry, intracellular calcium chelation (BAPTA-AM), PP2 Src kinase inhibition, aspirin treatment, G-protein pathway-selective agonists, P2Y1-deficient and Galpha(q)-deficient mouse platelets Blood High 15546949
2003 CBFA2 (RUNX1) mutation in a patient is associated with decreased platelet PKC-theta and impaired receptor-mediated GPIIb-IIIa activation and pleckstrin phosphorylation, demonstrating that PKC-theta and proteins regulated by CBFA2 are required for inside-out signal transduction leading to GPIIb-IIIa activation. Platelet RNA sequencing (exon amplification), immunoblotting for PKC isoforms and pleckstrin, flow cytometry for GPIIb-IIIa activation (PAC-1), functional aggregation assays Blood Medium 14525764
2005 ADAM15 (metargidin) functions as an adhesion receptor for platelet GPIIb-IIIa. Soluble ADAM15 binds to activated but not resting GPIIb-IIIa. Platelet adhesion to immobilized ADAM15 is blocked by anti-alphaIIbbeta3 mAbs (7E3, 2G12) but not by anti-alphavbeta3 (LM609). Adhesion to ADAM15 triggers platelet activation including CD62P secretion and CD40L release. Platelet adhesion assay under static and shear conditions, neutralizing anti-integrin mAbs, flow cytometry for activation markers (CD62P, CD40L), ADAM15 overexpression on endothelial cells Thrombosis and haemostasis Medium 16268472
2006 S. aureus fibronectin-binding proteins FnBPA and FnBPB activate platelets via two distinct bridges to the low-affinity form of GPIIb/IIIa on resting platelets: (i) fibrinogen bridging to the A domain and (ii) fibronectin bridging to the BCD region. Antibodies recognizing FnBPA engage platelet FcgammaRIIa to complete activation; blocking GPIIb/IIIa or FcgammaRIIa (mAb IV-3) inhibits activation. Platelet aggregation assays, domain-truncation constructs of FnBPA expressed on S. aureus and L. lactis, blocking antibodies against GPIIb/IIIa and FcgammaRIIa Molecular microbiology High 16359330
2007 Platelet-derived microparticles (PMPs) transfer functional GPIIb/IIIa receptors to neutrophils. On GM-CSF-treated neutrophils, acquired GPIIb/IIIa co-localizes with beta2-integrins and cooperates with them to activate NF-kappaB via Src, Syk, and the actin cytoskeleton. Blocking either beta2-integrins or GPIIb/IIIa abrogates fibronectin-induced NF-kappaB activation and TNF-alpha mRNA upregulation in PMP-loaded neutrophils. Flow cytometry and confocal microscopy for receptor surface expression, NF-kappaB Western blot and EMSA, RT-PCR for TNF-alpha, kinase inhibitors (Src, Syk), blocking antibodies, therapeutic GPIIb/IIIa inhibitors The Journal of biological chemistry Medium 17644514
2011 A heterozygous ITGA2B R995W (αIIb-W995) mutation induces constitutive activation of the αIIbβ3 receptor as shown by spontaneous PAC-1 and fibrinogen binding to resting platelets, and spontaneous FAK phosphorylation in transfected 293T cells. The activated αIIb-W995/β3 causes membrane ruffling and abnormal cytoplasmic protrusions in transfected CHO cells, and increases proplatelet tip size/decreases tip number in mouse fetal liver-derived megakaryocytes, establishing a mechanism for congenital macrothrombocytopenia. Flow cytometry (PAC-1, fibrinogen binding), FAK phosphorylation by Western blot, 293T and CHO cell transfection with mutant constructs, mouse fetal liver megakaryocyte transduction, proplatelet formation assay Blood High 21454453
2012 Itga2b expression in hematopoietic cells is regulated by lineage-specific epigenetic mechanisms: H4K8 acetylation marks the locus in megakaryocytes, while H3K27me3 represses it in multipotential hematopoietic progenitors (HPC7 cells). Commitment to megakaryocyte differentiation is accompanied by upregulation of the H3K27 demethylase Jmjd3, which correlates with decreased H3K27me3 at the Itga2b locus and increased CD41 expression. An internal promoter mechanism also participates in developmental regulation. Chromatin immunoprecipitation (H4K8ac, H3K27me3), RT-PCR for Jmjd3 and Itga2b, promoter analysis in multiple hematopoietic cell contexts PloS one Medium 22952660
2023 Integrin GPIIb (αIIb)-dependent outside-in signaling via Gα13 coordinates platelet polarization during migration by triggering a c-Src/14-3-3ζ-dependent lamellipodium formation pathway. This pathway is independent of soluble agonists or chemotactic signals and requires anisotropic myosin IIa activity at the platelet rear preceded by polarized actin polymerization at the front. Dasatinib (ABL/c-Src inhibitor) and other inhibitors of this cascade selectively impair platelet migration without major effects on classical platelet functions. Time-resolved morphodynamic profiling of individual platelets, pharmacologic inhibitors (dasatinib and others), murine inflammation models with 4D intravital microscopy, patient platelets from dasatinib-treated leukemia patients, actin/myosin perturbation experiments Blood High 37018659
2020 CD41 (integrin α2b) in exosomes activates a CD41-integrin β3-FAK-Akt-Runx2 signaling pathway to support osteogenic differentiation and migration of mesenchymal stem cells. Exosomes from osteonecrosis of the femoral head (ONFH) tissue are deficient in CD41, and downregulation of CD41 in normal exosomes impairs this pathway and reduces MSC osteogenic differentiation and migration. Proteomic analysis of ONFH exosomes vs. normal exosomes, siRNA knockdown of CD41 in MSCs, Western blot for FAK/Akt/Runx2 phosphorylation, osteogenic differentiation assays, migration assays, rat in vivo ONFH model Cell death & disease Medium 32341357
1988 A GPIIb-IIIa-related protein in endothelial cells localizes to vinculin-rich focal contacts at stress fiber membrane insertions and to cell-to-cell contacts. Anti-GPIIb-IIIa antibodies added to endothelial cell suspensions inhibit spreading on fibrinogen and vitronectin substrata but are poorly active on fibronectin; antibodies added to adherent cells disrupt cell-to-cell contacts and cause rounding and detachment. Immunofluorescence localization, polyclonal anti-GPIIb-IIIa antibody inhibition of endothelial cell spreading on different matrix substrates, antibody-induced detachment assay Blood Medium 3345337
1990 When platelets are treated with monoclonal antibodies Tab (anti-GPIIb) and AP3 (anti-GPIIIa) together and stimulated with ADP, they form short blunted projections instead of normal filopodia, sequester GPIIb-IIIa and fibrinogen into the surface-connected canalicular system via massive actomyosin-controlled membrane flow, and fail to aggregate despite normal fibrinogen binding. This indicates that GPIIb-IIIa plays a role in signaling cytoskeletal rearrangements required for filopodium formation and aggregation. Scanning and transmission electron microscopy, immunolabel-surface replication, immunocytochemistry on frozen sections, biochemical cytoskeletal activation assays, platelet aggregometry Blood Medium 2207330
1995 During platelet spreading, GPIIb-IIIa complexes pre-labeled with fibrinogen-coated gold particles translocate from uniform surface distribution to caps over cell centers and into channels of the open canalicular system (OCS), while GPIb/IX pre-labeled with vWF moves with the expanding cell membrane toward peripheral margins. These two receptor populations thus undergo distinct directional redistribution during spreading. Pre-labeling of discoid platelets with fibrinogen-coated gold or vWF/protein A-gold, electron microscopy, immunolabel-surface replication, cytochalasin E treatment to preserve discoid shape British journal of haematology Medium 7647005
2022 Cooperative signaling of platelet CLEC-2 and GPIIb/IIIa triggers cerebral venous sinus thrombosis (CVT)-like syndrome in mice within minutes. Pharmacological inhibition of GPIIb/IIIa (or CLEC-2 signaling) completely blocks platelet activation and CVT, and GPIIb/IIIa blockade after onset of neurological symptoms rescues mice from platelet consumption and death, demonstrating a mechanistic role for GPIIb/IIIa in pathological platelet activation underlying CVT. Antibody-induced mouse CVT model (INU1-fab), intravital transcranial microscopy, pharmacologic GPIIb/IIIa inhibition, CLEC-2 signaling blockade, heparin comparison, brain autopsy Nature cardiovascular research High 39195988
2005 GPIIb (CD41) integrin is expressed on cultured bone marrow mast cells (human and murine). Loss of GPIIb in gpIIb-/- mice does not affect mast cell growth or differentiation markers but results in altered adhesion to fibronectin- and vitronectin-coated surfaces and increased surface expression of αV integrin as a compensatory response. Flow cytometry of bone marrow mast cells from wild-type and gpIIb-/- mice, adhesion assays on matrix-coated surfaces, analysis of peritoneal mast cells in vivo Experimental hematology Medium 15781330

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 Platelet GPIIb-IIIa blockers. Lancet (London, England) 409 9923894
2005 Analysis of thrombocyte development in CD41-GFP transgenic zebrafish. Blood 320 16099879
2002 Expression of CD41 marks the initiation of definitive hematopoiesis in the mouse embryo. Blood 298 12393529
2008 The GPIIb/IIIa (integrin alphaIIbbeta3) odyssey: a technology-driven saga of a receptor with twists, turns, and even a bend. Blood 279 18840725
2013 CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age. Blood 276 23564910
2003 CD41 expression defines the onset of primitive and definitive hematopoiesis in the murine embryo. Development (Cambridge, England) 263 12900455
2002 Multiple roles for platelet GPIIb/IIIa and alphavbeta3 integrins in tumor growth, angiogenesis, and metastasis. Cancer research 195 12019160
2008 CD41+ cmyb+ precursors colonize the zebrafish pronephros by a novel migration route to initiate adult hematopoiesis. Development (Cambridge, England) 182 18417622
2011 Glanzmann thrombasthenia: a review of ITGA2B and ITGB3 defects with emphasis on variants, phenotypic variability, and mouse models. Blood 176 21917754
2006 Fibronectin-binding proteins of Staphylococcus aureus mediate activation of human platelets via fibrinogen and fibronectin bridges to integrin GPIIb/IIIa and IgG binding to the FcgammaRIIa receptor. Molecular microbiology 165 16359330
2001 Anti-GPIIb/IIIa drugs: current strategies and future directions. Thrombosis and haemostasis 143 11487034
2002 Expression of CD41 on hematopoietic progenitors derived from embryonic hematopoietic cells. Development (Cambridge, England) 133 11934866
2003 Inhibition of tumor cell-induced platelet aggregation and lung metastasis by the oral GpIIb/IIIa antagonist XV454. Thrombosis and haemostasis 121 12958625
1995 New antiplatelet agents: platelet GPIIb/IIIa antagonists. Thrombosis and haemostasis 117 8578476
1997 GPIIb/IIIa antagonists: pathophysiologic and therapeutic insights from studies of c7E3 Fab. Thrombosis and haemostasis 112 9198247
1987 Biosynthesis and processing of platelet GPIIb-IIIa in human megakaryocytes. The Journal of cell biology 96 3108266
1989 Biosynthesis and assembly of platelet GPIIb-IIIa in human megakaryocytes: evidence that assembly between pro-GPIIb and GPIIIa is a prerequisite for expression of the complex on the cell surface. Blood 94 2477081
1991 Tissue-specific expression of the platelet GPIIb gene. The Journal of biological chemistry 92 2026605
2012 GPIIb/IIIa inhibitors: from bench to bedside and back to bench again. Thrombosis and haemostasis 85 22370973
2011 Heterozygous ITGA2B R995W mutation inducing constitutive activation of the αIIbβ3 receptor affects proplatelet formation and causes congenital macrothrombocytopenia. Blood 77 21454453
1995 Characterization of tumor-induced platelet aggregation: the role of immunorelated GPIb and GPIIb/IIIa expression by MCF-7 breast cancer cells. Thrombosis research 77 8533122
1999 Quantifying GPIIb/IIIa receptor binding using 2 monoclonal antibodies: discriminating abciximab and small molecular weight antagonists. Circulation 76 10226086
2015 Expanding the Mutation Spectrum Affecting αIIbβ3 Integrin in Glanzmann Thrombasthenia: Screening of the ITGA2B and ITGB3 Genes in a Large International Cohort. Human mutation 70 25728920
2005 Endothelial cells in the early murine yolk sac give rise to CD41-expressing hematopoietic cells. Stem cells and development 70 15725743
2001 Different expression of CD41 on human lymphoid and myeloid progenitors from adults and neonates. Blood 67 11264167
2003 Association of CBFA2 mutation with decreased platelet PKC-theta and impaired receptor-mediated activation of GPIIb-IIIa and pleckstrin phosphorylation: proteins regulated by CBFA2 play a role in GPIIb-IIIa activation. Blood 62 14525764
2007 Beta2-integrins and acquired glycoprotein IIb/IIIa (GPIIb/IIIa) receptors cooperate in NF-kappaB activation of human neutrophils. The Journal of biological chemistry 61 17644514
1999 Blockade of GpIIb/IIIa inhibits the release of vascular endothelial growth factor (VEGF) from tumor cell-activated platelets and experimental metastasis. Platelets 60 16801104
1998 In vitro hypothermia enhances platelet GPIIb-IIIa activation and P-selectin expression. Anesthesiology 58 9637652
1991 Anti-GPIIb/IIIa (CD41) monoclonal antibody-induced platelet activation requires Fc receptor-dependent cell-cell interaction. British journal of haematology 55 1832937
2011 CD41 is developmentally regulated and differentially expressed on mouse hematopoietic stem cells. Blood 54 21415271
1988 The localization of a platelet GpIIb-IIIa-related protein in endothelial cell adhesion structures. Blood 53 3345337
2004 Oral GPIIb/IIIa antagonists: what went wrong? Current pharmaceutical design 52 15134557
1999 Platelet integrin GPIIb/IIIa: structure-function correlations. An update and lessons from other integrins. Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.) 52 10510244
2011 Delineating the roles of the GPIIb/IIIa and GP-Ib-IX-V platelet receptors in mediating platelet adhesion to adsorbed fibrinogen and albumin. Biomaterials 49 21529934
2010 Antagonism of P2Y12 or GPIIb/IIIa receptors reduces platelet-mediated myocardial injury after ischaemia and reperfusion in isolated rat hearts. Thrombosis and haemostasis 49 20431845
2005 GPIIb-IIIa antagonists reduce thromboinflammatory processes in patients with acute coronary syndromes undergoing percutaneous coronary intervention. Journal of thrombosis and haemostasis : JTH 46 15670038
2004 Extracellular signal-regulated kinase induces the megakaryocyte GPIIb/CD41 gene through MafB/Kreisler. Molecular and cellular biology 45 15121870
2003 Formation of disulfide-linked complexes between the three minor envelope glycoproteins (GP2b, GP3, and GP4) of equine arteritis virus. Journal of virology 45 12743278
1987 Quinine- and quinidine platelet antibodies can react with GPIIb/IIIa. British journal of haematology 45 3676108
2010 Targeting the platelet integrin GPIIb/IIIa. Current pharmaceutical design 43 21247395
2009 Molecular defects in ITGA2B and ITGB3 genes in patients with Glanzmann thrombasthenia. Journal of thrombosis and haemostasis : JTH 43 19691478
2006 Molecular diversity of Glanzmann thrombasthenia in southern India: new insights into mRNA splicing and structure-function correlations of alphaIIbbeta3 integrin (ITGA2B, ITGB3). Human mutation 43 16463284
2005 ADAM 15 is an adhesion receptor for platelet GPIIb-IIIa and induces platelet activation. Thrombosis and haemostasis 43 16268472
2002 Anti-platelet effects of GPIIb/IIIa and P-selectin antagonism, platelet activation, and binding to neutrophils. Journal of cardiovascular pharmacology 43 12131559
2004 Differential requirements for calcium and Src family kinases in platelet GPIIb/IIIa activation and thromboxane generation downstream of different G-protein pathways. Blood 40 15546949
1992 Role of the transmembrane and cytoplasmic domains in the assembly and surface exposure of the platelet integrin GPIIb/IIIa. Biochemistry 40 1540596
1990 GPIIb and GPIIIa amino acid sequences deduced from human megakaryocyte cDNAs. Molecular biology reports 40 2345548
2014 Runx1 is required for progression of CD41+ embryonic precursors into HSCs but not prior to this. Development (Cambridge, England) 38 25139854
2008 Modulation of murine embryonic stem cell-derived CD41+c-kit+ hematopoietic progenitors by ectopic expression of Cdx genes. Blood 38 18252864
1992 Increased GPIIB/IIIA expression and altered DNA-ploidy pattern in megakaryocytes of diabetic BB-rats. European journal of clinical investigation 37 1459176
2020 CD41-deficient exosomes from non-traumatic femoral head necrosis tissues impair osteogenic differentiation and migration of mesenchymal stem cells. Cell death & disease 36 32341357
2000 Potential future clinical applications for the GPIIb/IIIa antagonist, abciximab in thrombosis, vascular and oncological indications. Pathology oncology research : POR 36 11033455
2015 CD41 marks the initial myelo-erythroid lineage specification in adult mouse hematopoiesis: redefinition of murine common myeloid progenitor. Stem cells (Dayton, Ohio) 35 25446279
2003 Reversibility versus persistence of GPIIb/IIIa blocker-induced conformational change of GPIIb/IIIa (alphaIIbbeta3, CD41/CD61). The Journal of pharmacology and experimental therapeutics 35 14617694
2009 The roles of platelet GPIIb/IIIa and alphavbeta3 integrins during HeLa cells adhesion, migration, and invasion to monolayer endothelium under static and dynamic shear flow. Journal of biomedicine & biotechnology 34 19888429
2021 Specifications of the variant curation guidelines for ITGA2B/ITGB3: ClinGen Platelet Disorder Variant Curation Panel. Blood advances 32 33496739
2010 AlphaIIbbeta3 integrin: new allelic variants in Glanzmann thrombasthenia, effects on ITGA2B and ITGB3 mRNA splicing, expression, and structure-function. Human mutation 31 20020534
2003 Intra- and intermolecular disulfide bonds of the GP2b glycoprotein of equine arteritis virus: relevance for virus assembly and infectivity. Journal of virology 31 14645556
1996 The anti-GPIIb-IIIa agents: fundamental and clinical aspects. Haemostasis 31 8979134
2007 Distinct hemogenic potential of endothelial cells and CD41+ cells in mouse embryos. Development, growth & differentiation 30 17501906
2000 Differential expression of a ligand induced binding site (LIBS) by GPIIb-IIIa ligand recognition peptides and parenteral antagonists. Thrombosis and haemostasis 30 11154119
1991 Activation-independent exposure of the GPIIb-IIIa fibrinogen receptor. Thrombosis research 30 1957276
2012 Itga2b regulation at the onset of definitive hematopoiesis and commitment to differentiation. PloS one 29 22952660
2000 Structure and function of murine alphaIIbbeta3 (GPIIb/IIIa): studies using monoclonal antibodies and beta3-null mice, Thrombosis and haemostasis 28 11154120
1990 Monoclonal antibodies bound to subunits of the integrin GPIIb-IIIa are internalized and interfere with filopodia formation and platelet aggregation. Blood 28 2207330
1993 Platelet GPIIb/IIIa receptor inhibition by SC-49992 prevents thrombosis and rethrombosis in the canine carotid artery. Cardiovascular research 27 8490951
2000 Interleukin-6 and interleukin-11 act synergistically with thrombopoietin and stem cell factor to modulate ex vivo expansion of human CD41+ and CD61+ megakaryocytic cells. Haematologica 26 10629587
1999 Cytokine-induced expansion of human CD34+ stem/progenitor and CD34+CD41+ early megakaryocytic marrow cells cultured on normal osteoblasts. Stem cells (Dayton, Ohio) 26 10195569
2023 Mechanosensing via a GpIIb/Src/14-3-3ζ axis critically regulates platelet migration in vascular inflammation. Blood 25 37018659
2005 GPIIb (CD41) integrin is expressed on mast cells and influences their adhesion properties. Experimental hematology 25 15781330
2003 Comparison of the effects of cellulose triacetate and polysulfone membrane on GPIIb/IIIa and platelet activation. Blood purification 25 12601261
1999 Antiplatelet therapies: from aspirin to GPIIb/IIIa-receptor antagonists and beyond. Drug discovery today 25 10557137
2009 Regulation of CD40L (CD154) and CD62P (p-selectin) surface expression upon GPIIb-IIIa blockade of platelets from stable coronary artery disease patients. Thrombosis research 23 19487018
1996 A nonsense mutation in the GPIIb heavy chain (Ser 870-->stop) impairs platelet GPIIb-IIIa expression. British journal of haematology 22 8904900
2022 Foudroyant cerebral venous (sinus) thrombosis triggered through CLEC-2 and GPIIb/IIIa dependent platelet activation. Nature cardiovascular research 21 39195988
2006 Cord blood in vitro expanded CD41 cells: identification of novel components of megakaryocytopoiesis. Journal of thrombosis and haemostasis : JTH 21 16634756
2008 Platelet GPIIb/IIIa receptor antagonists in human ischemic brain disease. Current vascular pharmacology 20 18220937
2008 Inhibition of platelet GPIIb-IIIa and P-selectin expression by aspirin is impaired by stress hyperglycemia. Journal of diabetes and its complications 20 18413191
1995 Redistribution of GPIb/IX and GPIIb/IIIa during spreading of discoid platelets. British journal of haematology 20 7647005
2022 TLR4 inhibitor alleviates sepsis-induced organ failure by inhibiting platelet mtROS production, autophagy, and GPIIb/IIIa expression. Journal of bioenergetics and biomembranes 19 35676565
2014 CD41 is a reliable identification and activation marker for murine basophils in the steady state and during helminth and malarial infections. European journal of immunology 19 24610714
2001 CD41+ and CD42+ hematopoietic progenitor cells may predict platelet engraftment after allogeneic peripheral blood stem cell transplantation. Journal of clinical apheresis 19 11746531
2015 The Src tyrosine kinase Lck binds to CD2, CD4-1, and CD4-2 T cell co-receptors in channel catfish, Ictalurus punctatus. Molecular immunology 18 25771179
2014 Thrombopoietin/MPL signaling confers growth and survival capacity to CD41-positive cells in a mouse model of Evi1 leukemia. Blood 17 25298035
2004 Thrombocytopenia resulting from sensitivity to GPIIb-IIIa inhibitors. Seminars in thrombosis and hemostasis 17 15497099
1998 In vitro expansion of CD34+/CD41+ cells from human peripheral blood CD34+/CD41- cells: role of cytokines for in vitro proliferation and differentiation of megakaryocytic progenitors. Experimental hematology 17 9808053
2019 Vincristine-loaded platelets coated with anti-CD41 mAbs: a new macrophage targeting proposal for the treatment of immune thrombocytopenia. Biomaterials science 16 31414106
2007 CD41+/CD45+ cells without acetylcholinesterase activity are immature and a major megakaryocytic population in murine bone marrow. Stem cells (Dayton, Ohio) 16 17420226
2002 Tirofiban blocks platelet adhesion to fibrin with minimal perturbation of GpIIb/IIIa structure. Thrombosis and haemostasis 16 12038797
2025 Synergistic anti-oxidative/anti-inflammatory treatment for acute lung injury with selenium based chlorogenic acid nanoparticles through modulating Mapk8ip1/MAPK and Itga2b/PI3k-AKT axis. Journal of nanobiotechnology 15 39849453
2015 Internalization of Tissue Factor-Rich Microvesicles by Platelets Occurs Independently of GPIIb-IIIa, and Involves CD36 Receptor, Serotonin Transporter and Cytoskeletal Assembly. Journal of cellular biochemistry 15 26221761
2014 Association of platelet ITGA2B and ITGB3 polymorphisms with ex vivo antiplatelet effect of ticagrelor in healthy Chinese male subjects. International journal of hematology 15 24474638
2004 The anti-platelet approach targeting the fibrinogen ligand of the GPIIB/IIIa receptor. Journal of peptide science : an official publication of the European Peptide Society 15 15526708
1989 Bone marrow and tissue expression of gpIIb/IIIa, LFA-1, Mac-1 and gp150,95 glycoproteins. European journal of haematology 15 2645166
2000 Ex vivo expansion of CD34+/CD41+ late progenitors from enriched peripheral blood CD34+ cells. Annals of hematology 14 10663616
1999 Increased serotonin receptor density and platelet GPIIb/IIIa activation among smokers. Arteriosclerosis, thrombosis, and vascular biology 14 10073984
1998 Novel technetium-99m-labeled platelet GPIIb/IIIa receptor antagonists as potential imaging agents for venous and arterial thrombosis. Coronary artery disease 14 9647415
2019 Novel Murine Model of Immune Thrombocytopaenia through Immunized CD41 Knockout Mice. Thrombosis and haemostasis 13 30630213
1999 Expression of CD41 and c-mpl does not indicate commitment to the megakaryocyte lineage during haemopoietic development. British journal of haematology 13 10554819

Missed literature

Know a paper Affinage missed for ITGA2B? Flag it for the maintainers and the community.

No submissions yet.