ArticleAmerican journal of physiology. Cell physiology2013
The PAK system links Rho GTPase signaling to thrombin-mediated platelet activation.
Article in American journal of physiology. Cell physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
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Who cites it
29 citing papers in PubMed, 50 citations in OpenAlex.
- RAP1-RHO small GTPase cross-talk mediates integrindependent and -independent platelet procoagulant response.Haematologica · 2026Article
- Article
- Small-Molecule Disruptors of the Interaction between Calcium- and Integrin-Binding Protein 1 and Integrin αACS pharmacology & translational science · 2024Article
- Rho GTPase Signaling in Platelet Regulation and Implication for Antiplatelet Therapies.International journal of molecular sciences · 2023Review
- Article
- Brain-specific deletion of GIT1 impairs cognition and alters phosphorylation of synaptic protein networks implicated in schizophrenia susceptibility.Molecular psychiatry · 2022Article
- Acetyl-CoA Carboxylase Inhibitor CP640.186 Increases Tubulin Acetylation and Impairs Thrombin-Induced Platelet Aggregation.International journal of molecular sciences · 2021Article
- Pharmacologic targeting of Cdc42 GTPase by a small molecule Cdc42 activity-specific inhibitor prevents platelet activation and thrombosis.Scientific reports · 2021Article
- Article
- Turning Platelets Off and On: Role of RhoGAPs and RhoGEFs in Platelet Activity.Frontiers in cardiovascular medicine · 2021Review
- Interrogation of kinase genetic interactions provides a global view of PAK1-mediated signal transduction pathways.The Journal of biological chemistry · 2020Article
- Review
- The Era of Thromboinflammation: Platelets Are Dynamic Sensors and Effector Cells During Infectious Diseases.Frontiers in immunology · 2019Review
- Modulation of store-operated calcium entry and nascent adhesion by p21-activated kinase 1.Experimental & molecular medicine · 2018Article
- Morphometric analysis of spread platelets identifies integrin αScientific reports · 2018Article
- Assessment of roles for the Rho-specific guanine nucleotide dissociation inhibitor Ly-GDI in platelet function: a spatial systems approach.American journal of physiology. Cell physiology · 2017Article
- Leukaemia-associated Rho guanine nucleotide exchange factor (LARG) plays an agonist specific role in platelet function through RhoA activation.Thrombosis and haemostasis · 2016Article
- Rac1 regulates bacterial toxin-induced thrombin generation.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2016Article
- Heat shock protein 70 regulates platelet integrin activation, granule secretion and aggregation.American journal of physiology. Cell physiology · 2016Article
- Pseudorabies Virus US3 Protein Kinase Protects Infected Cells from NK Cell-Mediated Lysis via Increased Binding of the Inhibitory NK Cell Receptor CD300a.Journal of virology · 2016Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
Abstract
Regulation of the platelet actin cytoskeleton by the Rho family of small GTPases is essential for the proper maintenance of hemostasis. However, little is known about how intracellular platelet activation from Rho GTPase family members, including Rac, Cdc42, and Rho, translate into changes in platelet actin structures. To better understand how Rho family GTPases coordinate platelet activation, we identified platelet proteins associated with Rac1, a Rho GTPase family member, and actin regulatory protein essential for platelet hemostatic function. Mass spectrometry analysis revealed that upon platelet activation with thrombin, Rac1 associates with a set of effectors of the p21-activated kinases (PAKs), including GIT1, βPIX, and guanine nucleotide exchange factor GEFH1. Platelet activation by thrombin triggered the PAK-dependent phosphorylation of GIT1, GEFH1, and other PAK effectors, including LIMK1 and Merlin. PAK was also required for the thrombin-mediated activation of the MEK/ERK pathway, Akt, calcium signaling, and phosphatidylserine (PS) exposure. Inhibition of PAK signaling prevented thrombin-induced platelet aggregation and blocked platelet focal adhesion and lamellipodia formation in response to thrombin. Together, these results demonstrate that the PAK signaling system is a key orchestrator of platelet actin dynamics, linking Rho GTPase activation downstream of thrombin stimulation to PAK effector function, MAP kinase activation, calcium signaling, and PS exposure in platelets.
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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.