ArticleThe Journal of biological chemistry2008
Fibrinogen-elongated gamma chain inhibits thrombin-induced platelet response, hindering the interaction with different receptors.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed, 36 citations in OpenAlex.
- Trial
- Plasma-Based Proteomics Profiling of Patients with Hyperthyroidism after Antithyroid Treatment.Molecules (Basel, Switzerland) · 2020Trial
- From haemadin to haemanorm: Synthesis and characterization of full-length haemadin from the leech Haemadipsa sylvestris and of a novel bivalent, highly potent thrombin inhibitor (haemanorm).Protein science : a publication of the Protein Society · 2023Article
- Article
- Exogenous human α-Synuclein acts in vitro as a mild platelet antiaggregant inhibiting α-thrombin-induced platelet activation.Scientific reports · 2022Article
- γ' fibrinogen levels are associated with blood clot strength in traumatic brain injury patients.American journal of surgery · 2020Article
- Fibrin γ/γ' influences the secretion of fibrinolytic components and clot structure.BMC molecular and cell biology · 2019Article
- Interaction of the synthetic antithrombotic peptide P10 with thrombin: a spectroscopy study.RSC advances · 2019Article
- Thrombin Exosite Maturation and Ligand Binding at ABE II Help Stabilize PAR-Binding Competent Conformation at ABE I.Biochemistry · 2019Article
- Non-canonical proteolytic activation of human prothrombin by subtilisin fromThe Journal of biological chemistry · 2017Article
- Thrombin-induced platelet activation via PAR4: pivotal role for exosite II.Thrombosis and haemostasis · 2014Article
- GpIbα interacts exclusively with exosite II of thrombin.Journal of molecular biology · 2014Article
- Ligand binding to anion-binding exosites regulates conformational properties of thrombin.The Journal of biological chemistry · 2013Article
- Role of electrostatic interactions in binding of thrombin to the fibrinogen γ' chain.Biochemistry · 2012Article
- Unravelling the mechanism and significance of thrombin binding to platelet glycoprotein Ib.Thrombosis and haemostasis · 2010Review
- Long range communication between exosites 1 and 2 modulates thrombin function.The Journal of biological chemistry · 2009Article
- Biophysical investigation of GpIbalpha binding to thrombin anion binding exosite II.Biochemistry · 2009Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The expression of the elongated fibrinogen gamma chain, termed gamma', derives from alternative splicing of mRNA and causes an insertion sequence of 20 amino acids. This insertion domain interacts with the anion-binding exosite (ABE)-II of thrombin. This study investigated whether and how gamma' chain binding to ABE-II affects thrombin interaction with its platelet receptors, i.e. glycoprotein Ibalpha (GpIbalpha), protease-activated receptor (PAR) 1, and PAR4. Both synthetic gamma' peptide and fibrinogen fragment D*, containing the elongated gamma' chain, inhibited thrombin-induced platelet aggregation up to 70%, with IC(50) values of 42+/-3.5 and 0.47+/-0.03 microm, respectively. Solid-phase binding and spectrofluorimetric assays showed that both fragment D* and the synthetic gamma' peptide specifically bind to thrombin ABE-II and competitively inhibit the thrombin binding to GpIbalpha with a mean K(i) approximately 0.5 and approximately 35 microm, respectively. Both these gamma' chain-containing ligands allosterically inhibited thrombin cleavage of a synthetic PAR1 peptide, of native PAR1 molecules on intact platelets, and of the synthetic chromogenic peptide D-Phe-pipecolyl-Arg-p-nitroanilide. PAR4 cleavage was unaffected. In summary, fibrinogen gamma' chain binds with high affinity to thrombin and inhibits with combined mechanisms the platelet response to thrombin. Thus, its variations in vivo may affect the hemostatic balance in arterial circulation.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.