Hamostaseologie 2021; 41(03): 206-216
DOI: 10.1055/a-1476-7873
Review Article

Fine-Tuning of Platelet Responses by Serine/Threonine Protein Kinases and Phosphatases—Just the Beginning

Yavar Shiravand
1   Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy
,
Ulrich Walter
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
,
Kerstin Jurk
2   Center for Thrombosis and Hemostasis (CTH), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany
› Author Affiliations
Funding K.J. and U.W. are supported by the German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503).

Abstract

Comprehensive proteomic analyses of human and murine platelets established an extraordinary intracellular repertoire of signaling components, which control crucial functions. The spectrum of platelet serine/threonine protein kinases (more than 100) includes the AGC family (protein kinase A, G, C [PKA, PKG, PKC]), the mitogen-activated protein kinases (MAPKs), and others. PKA and PKG have multiple significantly overlapping substrates in human platelets, which possibly affect functions with clear “signaling nodes” of regulation by multiple protein kinases/phosphatases. Signaling nodes are intracellular Ca2+ stores, the contractile system (myosin light chains), and other signaling components such as G-proteins, protein kinases, and protein phosphatases. An example for this fine-tuning is the tyrosine kinase Syk, a crucial component of platelet activation, which is controlled by several serine/threonine and tyrosine protein kinases as well as phosphatases. Other protein kinases including PKA/PKG modulate protein phosphatase 2A, which may be a master regulator of MAPK signaling in human platelets. Protein kinases and in particular MAPKs are targeted by an increasing number of clinically used inhibitors. However, the precise regulation and fine-tuning of these protein kinases and their effects on other signaling components in platelets are only superficially understood—just the beginning. However, promising future approaches are in sight.

Supplementary Material



Publication History

Received: 23 December 2020

Accepted: 06 April 2021

Article published online:
30 June 2021

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