PAFR Membrane Protein Introduction

Introduction of PAFR

Platelet-activating factor receptor (PAFR) is encoded by the PTAFR gene. It belongs to the G-protein-coupled receptor (GPCR) family which is the largest family of receptors in the human genome. GPCRs play very important roles in medicine because of their large number, widespread distribution and important roles in cell physiology and biochemistry. PAFR belongs to the rhodopsin family and possesses seven transmembrane alpha helices as other GPCRs and uses platelet-activating factor (PAF) as the preferred endogenous ligand. Meanwhile, its structure reveals that the critical residues for ligand binding are located deep within the lipid bilayer.

Function of PAFR Membrane Protein

The activity of PAFR is mediated by its endogenous ligand, platelet-activating factor (PAF). The signaling pathway of PAF and PAFR have been shown to play role in modulating the angiogenesis, tumor cell adhesion, growth, and metastasis. The expression level of PAR-1 is upregulated significantly in malignant melanoma tumors compared to common melanocytic nevi. PAFR is also a potent mediator of tumor neoangiogenesis because numerous reports suggest that PAFR is involved in mediating angiogenesis and activating endothelial cells directly. PAFR antagonist PCA4248 inhibit the melanoma human lung metastasis potently when it comes to the in vivo experiments. More importantly, the daily treatments with PCA4248 show potent inhibition to the growth of established microscopic tumor cell colonies in the lungs. So, development the inhibitors against PAFR maybe act as a promising treatment for vascular dissemination or tumor/metastasis outgrowth. Meanwhile, the interaction between PAF and PAFR activate the Gαq and p38 MAPK signaling cascade, resulting in the overexpression and secretion of MMP-2 and MT1-MMP, which is important to respond to inflammatory stimulation from the tumor microenvironment.

Fig.1 PAFR intracellular signaling pathways (Melnikova, 2008).

Application of PAFR Membrane Protein in Literature

1. Melnikova V.O., et al. Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis. Cancer Microenvironment. 2008, 1(1):103-111. PubMed ID: 9308689
   
   

   This article reports the importance of PAR-1 as well as CREB/ATF-1 downstream of PAFR signaling pathway in responding to inflammatory stimulation from the tumor microenvironment as PAR-1 and PAFR are overexpressed in metastatic melanoma cells.

2. Yao B., et al. PAFR selectively mediates radioresistance and irradiation-induced autophagy suppression in prostate cancer cells. Oncotarget. 2017, 8(8):13846-13854. PubMed ID: 28099922
   
   

   This article reveals that PAFR induces autophagy suppression independent of activating mTOR pathway as PAFR can bind to the autophagy-indispensable protein Beclin 1, leading to the disability in its serine phosphorylation.

3. Sonia J., et al. PAF Receptor and Tumor Growth. Curr. Drug Targets. 2014, 15(10):982-987. PubMed ID: 25182608
   
   

   This article proposes that the combination of PAFR antagonists and chemotherapy may represent a promising strategy for cancer treatment because PAFR and ligands are upregulated in some tumor cells significantly.

4. Yu Y., et al. The expression of platelet-activating factor receptor modulates the cisplatin sensitivity of ovarian cancer cells: a novel target for combination therapy. Br. J. Cancer. 2014, 111(3):515-524. PubMed ID: 24921917
   
   

   This article suggests that PAFR is a novel and promising therapeutic target for sensitizing ovarian cancer cells to cisplatin because the PAFR expression is upregulated induced by cisplatin in two ovarian cancer cell lines.

5. Ishii S., et al. Platelet-activating factor receptor. Prostaglandins & Other Lipid Mediators. 2002, 68-69:599-609. PubMed ID: 12432946
   
   

   The authors in this article establish two different types of transgenic mice model, PAF receptor-overexpressing mouse, and PAF receptor-deficient mouse model and summarize the previous reports regarding PAF and PAF receptor.

PAFR Preparation Options

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Reference

1. Melnikova VO, et al. (2008). Emerging Roles of PAR-1 and PAFR in Melanoma Metastasis. Cancer Microenvironment. 1(1):103-111.

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