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GP6

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Glycoprotein VI (GP6), also known as GPVI 1, GPIV, platelet glycoprotein VI or platelet collagen receptor is a 339-amino acid type I transmembrane glycoprotein of the immunoglobulin superfamily with an estimated molecular weight of ~37.5 kDa and apparent m.w..of platelets in SDS-PAGE being between58-65kD due to extensive N-linked glycosylation. The activated GP6 forms a signaling complex with two copies of the non-covalently bound Fc receptor gamma-chain (FcRγ) in platelets via complementary charged residues present at their respective transmembrane domains, where an arginine existed in position 60 of GP6 and aspartic acid appeared for position 65 in FCyR. The FcRγ chain, which is linked to the receptor and carries an immunoreceptor tyrosine-based activation motif (ITAM) that undergoes phosphorylation upon engagement with ligand (data not shown), has a key role in signal transduction by initiating downstream signaling events through Src family kinases (Fyn/Lyn), Syk, LAT as well as phospholipase Cγ2(PLCγ2) followed by PI3K. With GP6 expression at a moderate density, pharmacological saturation is possible. Although the receptor itself is not directly involved in non-immunoglubulin-like cell adhesion, it does recognize collagen via its D1 domain using Gly-Pro-Hyp (GPO) peptide repeats within a triple-helical structure found in fibrillar collagens such as types I and III [21], both of which are enriched at sites of human advanced plaque development or injury-related vascular subendothelium. Beyond simple collagen, GP6 has now been defined as a more universal receptor with similar multi-ligand specificity including fibrin(ogen), laminin, fibronectin and vitronectin positioning it as an example of a pattern recognition receptor that connects the tissue factor-coagulation cascade activated by thrombogenic pathways during thrombus growth/stabilization. GP6 mutations are responsible for the autosomal-dominant bleeding disorder-11 (BDPLT11), which is characterized by defective collagen-induced platelet aggregation and a mild bleeding diathesis, while GP6 deficiency paradoxically protects against arterial thrombosis without clinically significant impairment of physiological hemostasis— an attractive safety profile that has propelled GP6 to prominence in antithrombotic drug development.

Fig.1 Antiplatelet activity through differential modulation of GP6 and its collagen binding. (OA Literature)Fig.1 Antiplatelet activity through differential modulation of glycoprotein VI and its collagen binding.1

GP6 Protein Function: A Central Orchestrator of Platelet Activation and Thrombus Dynamics

GP6 functional contributions span the full range of platelet biology from initial adhesion to thrombus consolidation:

  • Collagen-Induced Platelet Activation and Primary Hemostasis: GP6 is the main platelet-activating collagen receptor, it takes an early pivotal role in activating signaling pathways that lead to platelet degranulation, shape change, or aggregation at sites of vascular injury.
  • Thrombus Growth and Fibrin Stabilization: GP6 has been shown to support thrombus growth independently of collagen exposure by binding directly with fibrin(ogen). This binding site is adjacent to the collagen-binding pocket, and it recognizes regions of fibrinogen (as well as its metabolites fibrin, D-fragment, and D-dimer) that are ubiquitous in these substrates.
  • Membrane Dynamics and Tetraspanin Regulation: GP6 lateral diffusion is regulated by tetraspanin Tspan that organizes glycoproteins into specialized plasma membrane microdomains to modulate the clustering competency of GP6 for signaling efficiency. Tspan9 deficiency reduces GP6 lateral mobility by 50%, which inhibits collagen-induced aggregation and secretion despite normal surface expression. This active membrane-coupling mechanism underscores the importance of cytoskeletal organization in GP6-mediated responses during platelet activation.

GP6 Membrane Protein Product

Creative Biolabs offers an extensive range of premium GP6 membrane protein products for the structural and functional analysis of this platelet specific immunoglobulin superfamily receptor. Using our proprietary Membrane Protein technology, we can produce GP6 across a range of expression systems. These rigorously validated proteins are available for use as ELISA standards, immunoassay development tools, antibody generation and characterization reagents, binding assays to collagen molecules/models/purified adhesins/in situ tissues/cell lines; experimental links between mechanisms of functional platelet activation biology. These tools allow researchers to discriminate GP6 interactions with collagen, fibrin(ogen), laminin and the FcRγ signaling complex.

GP6 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

GP6 Stable Cell Line Product

Creative Biolabs manufactures proprietary GP6 membrane protein stable cell lines that consistently produce high target GP6 expression levels. These stable cell lines are excellent systems for drug screening, ligand binding studies and platelet activation assays as well as modelling of thrombus formation that can be readily developed to high throughput including the study of GP6 biology and pharmacology in a highly reproducible model system. With our knowledge, we guarantee you the best expression and cell integrity in order to speed up your research pipeline. We provide GP6-overexpressing lines useful for the elucidation of collagen and fibrin(ogen) binding mechanisms, and also GP6-knockdown lines facilitating loss-of-function studies with validated expression verified by flow cytometry, Western blotting or functional assays based on activation upon collagen-mediated stimulation. These ITAM-dependent luciferase readouts, in conjunction with specialized reporter systems cell lines to track GP6 signaling dynamics over time, will be useful when synergetically used during thrombosis and hemostasis models for basic mechanisms of therapeutic screening.

GP6 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

GP6 Recombinant Antibody Product

We offer a significant array of high-affinity recombinant antibodies specific for GP6 to support the needs of your most demanding research applications. These antibodies, developed utilizing emerging recombinant technologies, provide advantages of increased specificity and sensitivity with more reproducible batch-to-batch consistency over traditional polyclonal antibodies. Our range of GP6 recombinant antibodies are rigorously validated for Western Blotting (WB), ELISA, Flow Cytometry (FCM), Immunofluorescence (IF),Immunocytochemistry(ICC), immunohistochemistry(IHC) and Immunoprecipitation(IP). These reagents enable precise detection and quantification of GP6 in a variety of sample types including platelet lysates as well as megakaryocyte cultures; plasma samples ::plasma::and serum samples. We provide antibodies for the monomeric AND dimeric forms of GP6, supporting receptor state profiling and assessment of its competence to form dimers. Further reagents against the D1 collagen-binding domain, the D2 dimerization interface and FcRγ association site bolster detailed structure-function studies on GP6 with pharmacological modulation.

GP6 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom GP6 Membrane Protein and Antibody Discovery Services

In addition to our catalog products, Creative Biolabs also provides customized services for membrane protein and antibody discovery & development. With our vast expertise and advanced platforms we can help you with:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous GP6 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Is Creative Biolabs's GP6 products available for clinical or diagnostic use?

    No, all Creative Biolabs GP6 products/services are laboratory research use only (RUO), not for clinical diagnosis, prevention or treatment of any disease.

  2. What GP6 products does Creative Biolabs produce?

    We have a wide variety of products to support GP6 research, including recombinant GP6 membrane proteins in different formats (VLPs, mammalian membrane extracts, ECD-Fc fusions, monomeric/dimeric variants), stable cell lines expressing GP6 for overexpression and ITAM reporter functionality studies, high-affinity anti-GP6 antibodies targeting distinct epitopes.

  3. Do your GP6 antibodies cross-react with mouse and rat orthologs that are frequently used in pre-clinical models of thrombosis, hemostasis and megakaryopoiesis?

    Yes, the immunogen is derived from a highly conserved region of all mammalian species assuring a consistent detection in mouse and rat platelet & megakaryocyte preparations without huge amounts of need for different primary (species-specific) antibodies.

  4. Are there GP6 variants with known bleeding disorder–associated mutations, or substitutions in the collagen-binding interface for comparative ligand affinity, signaling threshold and trafficking studies?

    Yes, we provide recombinant proteins as well as stable cell lines that express characterized pathogenic substitutions in the immunoglobulin-like domain or transmembrane region leading to either disrupted collagen recognition (e.g., R75W) or partial loss of FcRγ coupling (S87C). These reagents allow direct comparison of ligand-binding kinetics, tyrosine kinase recruitment efficiency and granule secretion magnitude relative to wild-type benchmarks in defined cellular environments.

Reference
  1. Fuentes, Eduardo. "Modulation of glycoprotein VI and its downstream signaling pathways as an antiplatelet target." International Journal of Molecular Sciences 23.17 (2022): 9882. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/ijms23179882
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