Inositol phospholipid turnover in PAF transmembrane signalling

Abstract

In a variety of cells and tissues, platelet activating factor (PAF) stimulates phospholipase C catalyzed breakdown of phosphoinositides. This results in the generation of the second messengers, inositol trisphosphate and diglyceride. This process occurs independently of extracellular Ca2+. A number of PAF structural analogues, receptor antagonists and drugs have been utilized to pharmacologically probe the activation of phospholipase C. PAF stimulation of the phosphoinositide turnover was shown to be sensitive to pertussis toxin in some systems, but not in others. The involvement of guanine nucleotide binding protein(s) and tyrosine kinase(s) in this process have also been postulated. These developments give new insights into PAF-receptor function at the molecular level, and also provide leads towards a better understanding of the cellular responses to PAF.

Purification and Characterization of Platelet-activating Factor Acetylhydrolase II from Bovine Liver Cytosol

“…The enzyme belong to a novel serine esterase family: both the 29-and 30-kDa subunits have a catalytic serine residue (20). 3 In contrast, PAF acetylhydrolase II (in the peak II fraction) appears to be a monomeric enzyme. It is, however, too early to be absolutely certain that this is the case, as we could obtain only a sharp single peak of activity by gel filtration chromatography in the presence of a certain detergent (CHAPS).…”

“…[1][2][3][4][5]. PAF is produced by a variety of cells and tissues (6 -8), and its synthesis by a variety of mammalian cells has been examined and is known to be tightly regulated (9).…”

Go-protein α-Subunits Activate Mitogen-activated Protein Kinase via a Novel Protein Kinase C-dependent Mechanism

“…PAF mediates a variety of physiological effects, including increased expression of the c-fos and c-jun protooncogenes (33), increased neurite outgrowth in PC12 pheochromocytoma cells (34), elevation of intracellular Ca 2ϩ (35), and increased phosphoinositide hydrolysis (15). M 1 AChR has previously been shown to couple primarily to G q/11 (21,22), whereas our data demonstrate a coupling with G o to mediate mitogenic signaling.…”

Plasmin modulates the thrombin-evoked calcium response in C6 glioma cells

“…Platelet-activating factor (PAF) is produced by two independent enzymic pathways involving either structural modification of a membrane lipid or de novo synthesis from an O-alkyl analogue of a lysophosphatidic acid [12]. As a potent lipid mediator of cellular function, PAF induces a wide range of biological responses including activation of protein kinases, and stimulation of arachidonic acid and phosphoinositide metabolism [12][13][14][15]. PAF interacts through the sn-2 position of its acetyl moiety with a surface membrane receptor that is proteinase sensitive and appears to be coupled to a G-protein [12,[14][15][16]].…”