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

Yunfeng Chen, Zaverio M. Ruggeri, Xiaoping Du

Research output: Contribution to journalReview articlepeer-review

28 Scopus citations

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 phosphatidylserine exposure, and regulation of mitochondrial function. In particular, 14-3-3 interacts with several phosphoserine-dependent binding sites in the major platelet adhesion receptor, the glycoprotein Ib-IX complex (GPIb-IX), regulating its interaction with von Willebrand factor (VWF) and mediating VWF/GPIb-IX–dependent mechanosignal transduction, leading to platelet activation. The interaction of 14-3-3 with GPIb-IX also plays a critical role in enabling the platelet response to low concentrations of thrombin through cooperative signaling mediated by protease-activated receptors and GPIb-IX. The various functions of 14-3-3 in platelets suggest that it is a possible target for the treatment of thrombosis and inflammation.

Original languageEnglish (US)
Pages (from-to)2436-2448
Number of pages13
JournalBlood
Volume131
Issue number22
DOIs
StatePublished - May 31 2018
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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