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14-3-3 proteins in platelet biology and glycoprotein Ib-IX signaling

Yunfeng Chen, Zaverio M. Ruggeri and Xiaoping Du

Abstract

Members of the 14-3-3 family of proteins function as adapters/modulators that recognize phosphoserine/phosphothreonine-based binding motifs in many intracellular proteins and play fundamental roles in signal transduction pathways of eukaryotic cells. In platelets, 14-3-3 plays a wide range of regulatory roles in phosphorylation-dependent signaling pathways, including G-protein signaling, cAMP signaling, agonist-induced phosphatidyl-serine (PS) exposure and regulation of mitochondrial function. In particular, 14-3-3 inter-acts with several phosphoserine-dependent binding sites in the major platelet adhesion re-ceptor, the glycoprotein Ib-IX complex (GPIb-IX), regulating its interaction with von Wil-lebrand factor (VWF) and mediating VWF/GPIb-IX-dependent mechano-signal transduc-tion leading to platelet activation. The interaction of 14-3-3 with GPIb-IX also plays a crit-ical role in enabling the platelet response to low concentrations of thrombin through coop-erative signaling mediated by protease-activated receptors (PARs) and GPIb-IX. The vari-ous functions of 14-3-3 in platelets suggest that it is a possible target for the treatment of thrombosis and inflammation.

  • Submitted September 21, 2017.
  • Accepted March 25, 2018.