ArticleBlood2008
RGT, a synthetic peptide corresponding to the integrin beta 3 cytoplasmic C-terminal sequence, selectively inhibits outside-in signaling in human platelets by disrupting the interaction of integrin alpha IIb beta 3 with Src kinase.
Article in Blood, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 59 citations in OpenAlex.
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- Endoplasmic Reticulum Stress-Induced triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Downregulation Exacerbates Platelet Activation and Myocardial Infarction in Patients With Coronary Artery Disease.Journal of the American Heart Association · 2025Article
- Structure, signal transduction, activation, and inhibition of integrin αIIbβ3.Thrombosis journal · 2023Review
- Abivertinib inhibits megakaryocyte differentiation and platelet biogenesis.Frontiers of medicine · 2022Article
- Targeting the RT loop of Src SH3 in Platelets Prevents Thrombosis without Compromising Hemostasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet.Molecules (Basel, Switzerland) · 2021Article
- The role of Sphingomyelin synthase 2 (SMS2) in platelet activation and its clinical significance.Thrombosis journal · 2021Article
- Characterization of Procoagulant COAT Platelets in Patients with Glanzmann Thrombasthenia.International journal of molecular sciences · 2020Article
- Platelet integrin αIIbβ3: signal transduction, regulation, and its therapeutic targeting.Journal of hematology & oncology · 2019Review
- Roles of integrin β3 cytoplasmic tail in bidirectional signal transduction in a trans-dominant inhibition model.Frontiers of medicine · 2016Article
- Article
- Evaluation of targeting c-Src by the RGT-containing peptide as a novel antithrombotic strategy.Journal of hematology & oncology · 2015Article
- Nucleotide-binding oligomerization domain 2 receptor is expressed in platelets and enhances platelet activation and thrombosis.Circulation · 2015Article
- Article
- Platelet Activation and Thrombus Formation over IgG Immune Complexes Requires Integrin αIIbβ3 and Lyn Kinase.PloS one · 2015Article
- Targeting integrin and integrin signaling in treating thrombosis.Arteriosclerosis, thrombosis, and vascular biology · 2015Review
- The β isoform of the catalytic subunit of protein phosphatase 2B restrains platelet function by suppressing outside-in αII b β3 integrin signaling.Journal of thrombosis and haemostasis : JTH · 2014Article
- Modulation of platelet activation and thrombus formation using a pan-PI3K inhibitor S14161.PloS one · 2014Article
- JAM-A protects from thrombosis by suppressing integrin αIIbβ3-dependent outside-in signaling in platelets.Blood · 2012Article
- Article
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12 authors at 5 institutions in 3 countries.
Funding
Abstract
Mutational analysis has established that the cytoplasmic tail of the integrin beta 3 subunit binds c-Src (termed as Src in this study) and is critical for bidirectional integrin signaling. Here we show in washed human platelets that a cell-permeable, myristoylated RGT peptide (myr-RGT) corresponding to the integrin beta 3 C-terminal sequence dose-dependently inhibited stable platelet adhesion and spreading on immobilized fibrinogen, and fibrin clot retraction as well. Myr-RGT also inhibited the aggregation-dependent platelet secretion and secretion-dependent second wave of platelet aggregation induced by adenosine diphosphate, ristocetin, or thrombin. Thus, myr-RGT inhibited integrin outside-in signaling. In contrast, myr-RGT had no inhibitory effect on adenosine diphosphate-induced soluble fibrinogen binding to platelets that is dependent on integrin inside-out signaling. Furthermore, the RGT peptide induced dissociation of Src from integrin beta 3 and dose-dependently inhibited the purified recombinant beta 3 cytoplasmic domain binding to Src-SH3. In addition, phosphorylation of the beta 3 cytoplasmic tyrosines, Y(747) and Y(759), was inhibited by myr-RGT. These data indicate an important role for beta 3-Src interaction in outside-in signaling. Thus, in intact human platelets, disruption of the association of Src with beta 3 and selective blockade of integrin alpha IIb beta 3 outside-in signaling by myr-RGT suggest a potential new antithrombotic strategy.
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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.