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

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.

journal_name

Blood

journal_title

Blood

authors

Chen Y,Ruggeri ZM,Du X

doi

10.1182/blood-2017-09-742650

subject

Has Abstract

pub_date

2018-05-31 00:00:00

pages

2436-2448

issue

22

eissn

0006-4971

issn

1528-0020

pii

blood-2017-09-742650

journal_volume

131

pub_type

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