The human platelet-activating factor receptor gene (PTAFR) contains no introns and maps to chromosome 1

doi:10.1016/0888-7543(92)90162-L

Genomics

Volume 13, Issue 3, July 1992, Pages 832-834

https://doi.org/10.1016/0888-7543(92)90162-L Get rights and content

Abstract

Platelet-activating factor (PAF), a phospholipid, exhibits a variety of potent inflammatory bioactivities that are mediated by a specific cell surface receptor. The gene for the human PAF receptor (PTAFR) has been isolated by hybridization with a guinea pig probe. The coding sequence contains no intervening sequences. The encoded protein is highly homologous to the guinea pig PAF receptor (82% identity) and contains seven putative transmembrane domains. The PAF receptor therefore appears to be a member of the G protein coupled family of receptors and exhibits significant similarity to many members of the family. Analysis of somatic cell hybrids suggests that the PAF receptor is encoded by a single gene on human chromosome 1.

Reference (7)

ManiatisT. et al.
The isolation of structural genes from libraries of eucaryotic DNA
Cell
(1978)
SmithA.J.H.
DNA sequence analysis by primed synthesis
BarnesP.J. et al.
PAF and lung disease

There are more references available in the full text version of this article.

Cited by (39)

Epigenetic signatures in cardiac fibrosis: Focusing on noncoding RNA regulators as the gatekeepers of cardiac fibroblast identity
2024, International Journal of Biological Macromolecules
Cardiac fibroblasts play a pivotal role in cardiac fibrosis by transformation of fibroblasts into myofibroblasts, which synthesis and secrete a large number of extracellular matrix proteins. Ultimately, this will lead to cardiac wall stiffness and impaired cardiac performance. The epigenetic regulation and fate reprogramming of cardiac fibroblasts has been advanced considerably in recent decades. Non coding RNAs (microRNAs, lncRNAs, circRNAs) regulate the functions and behaviors of cardiac fibroblasts, including proliferation, migration, phenotypic transformation, inflammation, pyroptosis, apoptosis, autophagy, which can provide the basis for novel targeted therapeutic treatments that abrogate activation and inflammation of cardiac fibroblasts, induce different death pathways in cardiac fibroblasts, or make it sensitive to established pathogenic cells targeted cytotoxic agents and biotherapy. This review summarizes our current knowledge in this field of ncRNAs function in epigenetic regulation and fate determination of cardiac fibroblasts as well as the details of signaling pathways contribute to cardiac fibrosis. Moreover, we will comment on the emerging landscape of lncRNAs and circRNAs function in regulating signal transduction pathways, gene translation processes and post-translational regulation of gene expression in cardiac fibroblast. In the end, the prospect of cardiac fibroblasts targeted therapy for cardiac fibrosis based on ncRNAs is discussed.
Organ Failure Due to Systemic Injury in Acute Pancreatitis
2019, Gastroenterology
Citation Excerpt :
PAF production in inflammation is mediated by phospholipase A2, and it is degraded by PAF acetylhydrolase.140 Its receptor is a G-protein receptor.141 PAF has a broad range of effects, including increasing vascular permeability, worsening inflammation, and initiating cell death.142
Acute pancreatitis may be associated with both local and systemic complications. Systemic injury manifests in the form of organ failure, which is seen in approximately 20% of all cases of acute pancreatitis and defines “severe acute pancreatitis.” Organ failure typically develops early in the course of acute pancreatitis, but also may develop later due to infected pancreatic necrosis–induced sepsis. Organ failure is the most important determinant of outcome in acute pancreatitis. We review here the current understanding of the risk factors, pathophysiology, timing, impact on outcome, and therapy of organ failure in acute pancreatitis. As we discuss the pathophysiology of severe systemic injury, the distinctions between markers and mediators of severity are highlighted based on evidence supporting their causality in organ failure. Emphasis is placed on clinically relevant end points of organ failure and the mechanisms underlying the pathophysiological perturbations, which offer insight into potential therapeutic targets to treat.
Activation of human mast cells through the platelet-activating factor receptor
2010, Journal of Allergy and Clinical Immunology
Citation Excerpt :
We next confirmed expression of mRNA for PAFR (Fig 2, A) and its protein in PB-derived MCs using RT-PCR and Western blotting (Fig 2, B), respectively. We confirmed that the sequence of PAFR expressed on human MCs was identical to that previously reported (data not shown).22 We also confirmed the expression of PAFR in human bronchial MCs in bronchial biopsy specimens by using immunohistochemistry (Fig 2, C).
In human subjects platelet-activating factor (PAF) concentrations are markedly increased in the plasma after anaphylactic reactions, and these correlate strongly with the severity of the response. The mechanism for the systemic spread of mast cell (MC) activation in anaphylaxis is often assumed to relate to the hematogenous spread of allergen, but this is implausible, and amplification mechanisms need to be considered.
We have investigated the ability of PAF to induce human MC degranulation using skin, lung, and peripheral blood (PB)–derived cultured MCs and the signaling pathways activated in PB-derived MCs in response to PAF.
The expression of PAF receptor was investigated by means of RT-PCR and Western blot analysis. Cell-signaling pathways in PB-derived MCs in response to PAF were investigated by analyzing the effect of various inhibitors and the silencing of phospholipase C (PLC) mRNA on PAF-mediated histamine release.
We show for the first time that PAF induces histamine release from human lung MCs and PB-derived MCs but not skin MCs. Activation of PAF receptor–coupled G_αi leads to degranulation through PLCγ1 and PLCβ2 activation in human MCs. PAF-induced degranulation was rapid, being maximal at 5 seconds, and was partially dependent on extracellular Ca²⁺.
Our findings provide a mechanism whereby PAF mediates an amplification loop for MC activation in the generation of anaphylaxis.
Platelet-activating factor receptor
2002, Prostaglandins and Other Lipid Mediators
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a biologically active phospholipid mediator. Although PAF was named for its potential to induce platelet aggregation, intense investigations have elucidated potent biological actions of PAF in a broad range of cell types and tissues. PAF acts by binding to a unique G-protein-coupled seven transmembrane receptor, and activates multiple intracellular signaling pathways. In the last decade, we have identified the PAF receptor structures, intracellular signaling mechanisms, and genomic organizations. Recently, we found a single nucleotide polymorphism of the human PAF receptor (A224D) with an allele frequency of 7.8% in Japanese. Cells expressing this receptor exhibited the reduced cellular signaling, although the binding parameters remain unchanged. We have established two different types of genetically altered mice, i.e. PAF receptor-overexpressing mouse and PAF receptor-deficient mouse. These mutant mice provide a novel and specific approach for identifying the pathophysiological and physiological functions of PAF in vivo. This review focuses on phenotypes of these mutant mice and summarizes the previous reports regarding PAF and PAF receptor.
The pig platelet-activating factor receptor gene is expressed at the mRNA level in different tissues and is mapped to chromosome 6
2002, Animal Reproduction Science
After the pig platelet-activating factor receptor (PAFr) gene was cloned and sequenced, the chromosomal location of this gene was studied using a pig/rodent somatic cell hybrid panel containing 27 cell lines. The results indicated that the pig PAFr gene is located on SSC6q22-23. Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is thought to be very important in the animal reproductive processes. Its function is mediated through a membrane-bound receptor. Pig PAFr mRNA distribution in different tissues was tested using reverse transcription and PCR (RT–PCR) reactions. All tissues examined expressed PAFr. Using a pig PAFr gene DNA competitor, PAFr expression was quantificated. The pig PAFr mRNA expression level was estimated to be from 1×10² to 1.2×10⁴ copies of complementary DNA (cDNA) per 50 ng of total RNA. The highest level was found in lung, and the lowest in the skeletal muscle. These results demonstrated that PAFr was differentially expressed in pig tissues.
Platelet-activating factor (PAF) receptor and genetically engineered PAF receptor mutant mice
2000, Progress in Lipid Research
Platelet-activating factor (PAF, 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a biologically active phospholipid mediator. Although PAF was initially recognized for its potential to induce platelet aggregation and secretion, intense investigations have elucidated potent biological actions of PAF in a broad range of cell types and tissues, many of which also produce the molecule. PAF acts by binding to a unique G-protein-coupled seven transmembrane receptor. PAF receptor is linked to intracellular signal transduction pathways, including turnover of phosphatidylinositol, elevation in intracellular calcium concentration, and activation of kinases, resulting in versatile bioactions. On the basis of numerous pharmacological reports, PAF is thought to have many pathophysiological and physiological functions. Recently advanced molecular technics enable us not only to clone PAF receptor cDNAs and genes, but also generate PAF receptor mutant animals, i.e., PAF receptor-overexpressing mouse and PAF receptor-deficient mouse. These mutant mice gave us a novel and specific approach for identifying the pathophysiological and physiological functions of PAF. This review also describes the phenotypes of these mutant mice and discusses them by referring to previously reported pharmacological and genetical data.

View all citing articles on Scopus

View full text

The human platelet-activating factor receptor gene (PTAFR) contains no introns and maps to chromosome 1

Abstract

Cell

PAF and lung disease