Platelet-activating factor receptor.
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.
Ishii
Satoshi
S
Department of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, Japan. mame@m.u-tokyo.ac.jp
Nagase
Takahide
T
Shimizu
Takao
T
D000818:Animals; D001921:Brain / Q000378:metabolism; D006801:Humans; D010972:Platelet Activating Factor / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D012772:Shock, Septic / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D012867:Skin / Q000378:metabolism
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor