Transmembrane signalling and paf-acether biosynthesis.
Expression of lyso paf-acether (lyso paf):acetyl-CoA acetyltransferase and its activation above basal levels by specific agonists controls the rate of paf biosynthesis in proinflammatory cells. Acetyltransferase activation in these cells is due to the rapid postranslational modification of an inactive precursor by phosphorylation, most probably catalyzed by a cAMP-dependent kinase. However, the possibility exists that a calcium/calmodulin-dependent kinase can be implicated as well. Unlike murine cultured mast cells, human neutrophils form paf when stimulated with phorbol myristate acetate (PMA) or diacylglycerol. In both cell types, acetyltransferase is activated by PMA. Controversy exists as to whether PMA activates the remodeling pathway, i.e. the activation of phospholipase A2 and acetyltransferase, or the de novo route through CDPcholine cholinephosphotransferase action on alkylacetylglycerol. There is some indication that PKC might regulate paf biosynthesis. The implication of a GTP-regulated protein has also been postulated in signal transduction leading to paf formation in endothelial cells, neutrophils, and mast cells. The topography of paf formation is discussed in light of the subcellular distribution of acetyltransferase in neutrophils and Krebs II cells.
Ninio
E
E
Institut National de la Santé et de la Recherche Médical U200, Clamart, France.
Joly
F
F
D000123:Acetyltransferases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D006801:Humans; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000096:biosynthesis*; D015398:Signal Transduction
C029271:O-deacetyl platelet activating factor; D010972:Platelet Activating Factor; D000123:Acetyltransferases; C027628:acetyl-CoA-1-alkyl-2-lyso-sn-glycero-3-phosphocholine acetyltransferase; D010741:Phospholipases A; D054467:Phospholipases A2