PTAFR Membrane Protein Introduction

Introduction of PTAFR

Platelet-activating factor receptor (PTAFR) is a G-protein coupled receptor that binds platelet-activating factor (PAF). PAF is a phospholipid and exhibits a variety of potent inflammatory bioactivities. PTAFR contains seven putative transmembrane domains (7 TMs), amongst, the conserved proline in TM6 is crucial for intracellular trafficking of PTAFR. There are two N-glycosylation sites have been found in PTAFR. The abundant expression of PTAFR is detected in leukocytes, with less expression in undifferentiated eosinophilic or erythroleukemia cell lines.

Function of PTAFR Membrane Protein

As the ligand of PAFR, PAF undoubtedly functions as a mediator in diverse pathologic processes and biological pathways, including inflammation, allergy, asthma, septic shock, arterial thrombosis, and cardiovascular homeostasis as well as cancers, by binding to the G-protein-coupled PAFR. The most well-known function of PAFR in inflammation is based on PAF-induced pathological responses and prevention of the pathological conditions by PAFR antagonists. PAFR signaling participates in the trafficking of leucocytes and the generation of bronchospasms and inflammation in asthma. In addition, PAFR contributes to a pro-inflammatory environment in obstructive nephropathy, favoring the fibrotic process, renal dysfunction, and progressive organ failure. Recently, PAFR is shown to be involved in the clearance of apoptotic cells by macrophages. Recent studies show that PAFR plays vital roles in tumor neo-angiogenesis by activation of nuclear factor-κB (NF-κB).

Fig.1 Schematic representation of the S. pneumoniae-PAFR interactions. (Iovino, 2013)

Application of PTAFR Membrane Protein in Literature

1. Hyland I., et al. Progress in the Development of Platelet-Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases. ChemMedChem. 2018, 13(18): 1873-1884. PubMed ID: 30009544
   
   

   This article discusses the development and synthesis of new platelet-activating factor (PAF) and its receptor (PAFr) antagonists, structure-activity relationship studies, the biological activity of these molecules, and their therapeutic potential.

2. Cao C., et al. Structural basis for signal recognition and transduction by platelet-activating-factor receptor. Nat Struct Mol Biol. 2018, 25: 488-495. PubMed ID: 29808000
   
   

   The authors in this article use single-molecule FRET and cell-based functional assays to study the platelet-activating-factor receptor (PAFR) structures and suggest that the conformational change in the helical bundle is ligand-dependent and plays a critical role in PAFR activation, thus greatly extending knowledge about signaling by G-protein-coupled receptors.

3. Ocana J.A., et al. Platelet-Activating Factor-Induced Reduction in Contact Hypersensitivity Responses Is Mediated by Mast Cells via Cyclooxygenase-2-Dependent Mechanisms. J Immunol. 2018, 200: 4004-4011. PubMed ID: 29695417
   
   

   These results support the hypothesis that mast cell (MC) PAFR activation promotes the immunosuppressive effects of PAF in part through histamine- and PGE2-dependent mechanisms.

4. da Silva-Junior I.A., et al. Platelet-Activating Factor Receptor Ligands Protect Tumor Cells from Radiation-Induced Cell Death. Front Oncol. 2018, 8: 10. PubMed ID: 29459885
   
   

   The results of this article show that irradiation of carcinoma cells generates PAFR ligands that protect tumor cells from death and suggests that the combination of radiotherapy (RT) with a PAFR antagonist could be a promising strategy for cancer treatment.

5. da Silva Junior I.A., et al. Modulation of Tumor-Associated Macrophages (TAM) Phenotype by Platelet-Activating Factor (PAF) Receptor. J Immunol Res. 2017, 5482768. PubMed ID: 29445756
   
   

   This article suggests that in the tumor microenvironment, endogenous platelet-activating factor (PAF)-like activity molecules bind PAFR in macrophages which acquire an M2-like profile and this promotes tumor growth.

PTAFR Preparation Options

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Reference

1. Iovino F, et al. (2013). Signaling or binding: the role of the platelet-activating factor receptor in invasive pneumococcal disease. Cell Microbiol. 15: 870-881.

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