TY - JOUR
T1 - 14-3-3 proteins in platelet biology and glycoprotein Ib-IX signaling
AU - Chen, Yunfeng
AU - Ruggeri, Zaverio M.
AU - Du, Xiaoping
N1 - Funding Information:
This work was supported by National Institute of Health, National Heart, Lung, and Blood Institute grants HL-062350 (X.D.), HL-080264 (X.D.), HL-125356 (X.D.), HL132019 (principal investigator: Cheng Zhu), HL-117722 (Z.M.R.), and HL-135294 (Z.M.R.).
Funding Information:
The authors acknowledge Cheng Zhu, Woodruff School of Mechanical Engineering and Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, for participation in the writing of this review. This work was supported by National Institute of Health, National Heart, Lung, and Blood Institute grants HL-062350 (X.D.), HL-080264 (X.D.), HL-125356 (X.D.), HL132019 (principal investigator: Cheng Zhu), HL-117722 (Z.M.R.), and HL-135294 (Z.M.R.).
Publisher Copyright:
Copyright 2011 by The American Society of Hematology; all rights reserved.
PY - 2018/5/31
Y1 - 2018/5/31
N2 - 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.
AB - 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.
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U2 - 10.1182/blood-2017-09-742650
DO - 10.1182/blood-2017-09-742650
M3 - Review article
C2 - 29622550
AN - SCOPUS:85048073586
SN - 0006-4971
VL - 131
SP - 2436
EP - 2448
JO - Blood
JF - Blood
IS - 22
ER -