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Hamostaseologie 2019; 39(02): 140-151
DOI: 10.1055/s-0038-1675356
Review Article
Georg Thieme Verlag KG Stuttgart · New York

New Insights into Platelet Signalling Pathways by Functional and Proteomic Approaches

Kerstin Jurk
1   Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes-Gutenberg University Mainz, Mainz, Germany
,
Ulrich Walter
1   Center for Thrombosis and Hemostasis (CTH), University Medical Center, Johannes-Gutenberg University Mainz, Mainz, Germany
› Author Affiliations
Further Information

Publication History

30 June 2018

05 September 2018

Publication Date:
19 November 2018 (online)

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Abstract

As circulating sentinels of vascular integrity, platelets act as crucial haemostatic cells as well as important inflammatory and immune cells, whereas under pathological conditions platelets drive thrombotic as well as non-thrombotic diseases related to chronic inflammation. In addition, platelets serve as an important cellular model to study the biology and pharmacology of signal transduction pathways. Platelet inhibition and activation responses are mediated by multiple signalling networks, which are tightly regulated by balanced catalysis of protein phosphorylation and dephosphorylation through protein kinases and protein phosphatases, respectively. However, we are only at the beginning of understanding the complexity of interacting signalling pathways and their impact on platelet function. Here, we review current functional and proteomic approaches that lead to novel concepts of understanding the proteome, kinome and phosphatome of human platelets. A more in-depth understanding of both protein kinases and protein phosphatases using human platelets will contribute to evaluate their further diagnostic and therapeutic potential in inflammation- and immune-mediated diseases.

Zusammenfassung

Als zentrale Hämostasezellen kontrollieren Thrombozyten die vaskuläre Integrität und steuern chronische Entzündungsprozesse, die zu thrombotischen aber auch Thrombose unabhängigen Erkrankungen führen. Zudem stellen Thrombozyten ein wichtiges zelluläres Model dar, um die Biologie und Pharmakologie von Signaltransduktionswegen zu untersuchen. Multiple Signalnetzwerke bestimmen hemmende und aktivierende Prozesse der Thrombozytenfunktion, die durch eine balancierte Katalyse von Proteinkinase-abhängiger Phosphorylierung und Proteinphosphatase-abhängiger Dephosphorylierung reguliert werden. Dennoch stehen wir erst am Anfang, die Komplexität der interagierenden Signalwege und ihre Bedeutung für die Thrombozytenfunktion zu verstehen. Diese Übersicht stellt aktuelle funktionelle und proteombasierte Konzepte vor, die zu einem neuen Verständnis des Proteoms, Kinoms und Phosphatoms humaner Thrombozyten führen. Ein besseres Verständnis von Proteinkinasen und Proteinphosphatasen in humanen Thrombozyten trägt entscheidend zur Beurteilung ihres diagnostischen und therapeutischen Potenzials für entzündungs- und immunvermittelte Erkrankungen bei.

Keywords

platelet signalling - proteomics - protein kinases - protein phosphatases

Schlüsselwörter

Thrombozytensignaltransduktion - Proteomics - Proteinkinasen - Proteinphosphatasen
 

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