ArticleThe Journal of biological chemistry2013
Distinct role of Pyk2 in mediating thromboxane generation downstream of both G12/13 and integrin αIIbβ3 in platelets.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 21 citations in OpenAlex.
- A novel G13-RAPGEF2-RAP1 signaling pathway critical for platelet adhesion and aggregation.Blood · 2026Article
- The Efficacy of Intrathecal Platelet-Rich Plasma Administration in Alleviation of Chronic Neuropathic Pain in Rat Model.Molecular neurobiology · 2025Article
- Role of Prednisolone in Platelet Activation by Inhibiting TxAAnimals : an open access journal from MDPI · 2023Article
- Antiplatelet Effect of Daphnetin Is Regulated by cPLAInternational journal of molecular sciences · 2023Article
- The Predominant Role of Arrestin3 in General GPCR Desensitization in Platelets.Journal of clinical medicine · 2021Article
- Characterization of Integrin αIIbβ3-Mediated Outside-in Signaling by Protein Kinase Cδ in Platelets.International journal of molecular sciences · 2020Article
- Role of GRK6 in the Regulation of Platelet Activation through Selective G Protein-Coupled Receptor (GPCR) Desensitization.International journal of molecular sciences · 2020Article
- PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway: reply.Journal of thrombosis and haemostasis : JTH · 2018Article
- PDK1 governs thromboxane generation and thrombosis in platelets by regulating activation of Raf1 in the MAPK pathway.Journal of thrombosis and haemostasis : JTH · 2018Article
- GThe Journal of biological chemistry · 2017Article
- Role of focal adhesion tyrosine kinases in GPVI-dependent platelet activation and reactive oxygen species formation.PloS one · 2014Article
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
Abstract
Proline-rich tyrosine kinase 2 (Pyk2) is activated by various agonists in platelets. We evaluated the signaling mechanism and the functional role of Pyk2 in platelets by using pharmacological inhibitors and Pyk2-deficient platelets. We found that platelet aggregation and secretion in response to 2-methylthio-ADP (2-MeSADP) and AYPGKF were diminished in the presence of Pyk2 inhibitors or in Pyk2-deficient platelets, suggesting that Pyk2 plays a positive regulatory role in platelet functional responses. It has been shown that ADP-, but not thrombin-induced thromboxane (TxA2) generation depends on integrin signaling. Unlike ADP, thrombin activates G12/13 pathways, and G12/13 pathways can substitute for integrin signaling for TxA2 generation. We found that Pyk2 was activated downstream of both G12/13 and integrin-mediated pathways, and both 2-MeSADP- and AYPGKF-induced TxA2 generation was significantly diminished in Pyk2-deficient platelets. In addition, TxA2 generation induced by co-stimulation of Gi and Gz pathways, which is dependent on integrin signaling, was inhibited by blocking Pyk2. Furthermore, inhibition of 2-MeSADP-induced TxA2 generation by fibrinogen receptor antagonist was not rescued by co-stimulation of G12/13 pathways in the presence of Pyk2 inhibitor. We conclude that Pyk2 is a common signaling effector downstream of both G12/13 and integrin αIIbβ3 signaling, which contributes to thromboxane generation.
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