Posttranslational modifications of platelet adhesion receptors

Shukun Sun; Bao Qiao; Yu Han; Bailu Wang; Shujian Wei; Yuguo Chen

doi:10.1016/j.phrs.2022.106413

Posttranslational modifications of platelet adhesion receptors

Pharmacol Res. 2022 Sep:183:106413. doi: 10.1016/j.phrs.2022.106413. Epub 2022 Aug 23.

Authors

Shukun Sun¹, Bao Qiao¹, Yu Han¹, Bailu Wang², Shujian Wei³, Yuguo Chen⁴

Affiliations

¹ Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
² Clinical Trial Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China.
³ Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: weishujian@sdu.edu.cn.
⁴ Department of Emergency and Chest Pain Center, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Clinical Research Center for Emergency and Critical Care Medicine of Shandong Province, Institute of Emergency and Critical Care Medicine of Shandong University, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Key Laboratory of Cardiopulmonary-Cerebral Resuscitation Research of Shandong Province, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The Key Laboratory of Cardiovascular Remodeling and Function Research, Chinese Ministry of Education, Chinese Ministry of Health and Chinese Academy of Medical Sciences, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China; The State and Shandong Province Joint Key Laboratory of Translational Cardiovascular Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, China. Electronic address: chen919085@sdu.edu.cn.

PMID: 36007773
DOI: 10.1016/j.phrs.2022.106413

Abstract

Platelets play a key role in normal hemostasis, whereas pathological platelet adhesion is involved in various cardiovascular events. The underlying cause in cardiovascular events involves plaque rupture leading to subsequent platelet adhesion, activation, release, and eventual thrombosis. Traditional antithrombotic drugs often target the signal transduction process of platelet adhesion receptors by influencing the synthesis of some key molecules, and their effects are limited. Posttranslational modifications (PTMs) of platelet adhesion receptors increase the functional diversity of the receptors and affect platelet physiological and pathological processes. Antithrombotic drugs targeting PTMs of platelet adhesion receptors may represent a new therapeutic idea. In this review, various PTMs, including phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, lipidation, and proteolysis, of three platelet adhesion receptors, glycoprotein Ib-IX-V (GPIb-IX-V), glycoprotein VI (GPVI), and integrin α_IIbβ_3, are reviewed. It is important to comprehensively understand the PTMs process of platelet adhesion receptors.

Keywords: 5-Hydroxytryptamine (PubChem CID: 5202); ADAM10 (PubChem CID: 160713827); ADAM17 (PubChem CID: 160717634); Adenosine diphosphate (PubChem CID: 6022); Adenosine triphosphate (PubChem CID: 5957); Adhesion receptors; Calyculin A (PubChem CID: 5311365); Glycoprotein Ib-IX-V; Glycoprotein VI; Integrin α(IIb)β(3); PR619 (PubChem CID: 2817763); PYR41 (PubChem CID: 5335621); Phorbol myristate (PubChem CID: 18633279); Platelets; Posttranslational modification; Thromboxane A2 (PubChem CID: 5280497).

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Blood Platelets
Fibrinolytic Agents / pharmacology
Humans
Platelet Activation
Platelet Glycoprotein GPIb-IX Complex* / metabolism
Platelet Glycoprotein GPIb-IX Complex* / pharmacology
Protein Processing, Post-Translational
Thrombosis*
von Willebrand Factor / metabolism
von Willebrand Factor / pharmacology

Substances

Fibrinolytic Agents
Platelet Glycoprotein GPIb-IX Complex
adhesion receptor
von Willebrand Factor