Phospholipid methylation: a possible mechanism of signal transduction across biomembranes.
The conversion of phosphatidylethanolamine (PE) to phosphatidylcholine (PC) is catalyzed by two methyltransferases with S-adenosylmethionine as the methyl donor. PC formed by transmethylation is further metabolized by phospholipase A2. The synthesis and degradation of methylated phospholipids are involved in regulating the number of the beta-adrenergic receptors and their coupling to adenylate cyclase in rat reticulocytes, HeLa cells, and rat astrocytoma cells. Methylation of the phospholipids in these cells is stimulated by binding of agonists to the beta-adrenergic receptors. Accumulation of phosphatidyl-N-monomethylethanolamine causes an increase in membrane fluidity and enhances the coupling of the receptors to adenylate cyclase. Agents that inhibit phospholipid methylation decrease the number of receptors in intact HeLa cells, while increased phospholipid methylation unmasks cryptic receptors. Conversely, the degradation of methylated phospholipids appears to be closely associated with the desensitization of the beta-adrenergic receptors following prolonged stimulation with isoproterenol. Inhibition and stimulation of phospholipase A2 causes inhibition and stimulation of this desensitization process.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001254:Astrocytoma; D002460:Cell Line; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D008563:Membrane Lipids / Q000378:metabolism; D008566:Membranes / Q000378:metabolism*; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D050918:Phosphatidylethanolamine N-Methyltransferase; D010714:Phosphatidylethanolamines / Q000378:metabolism; D010740:Phospholipases / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D011943:Receptors, Adrenergic, beta / Q000502:physiology
D008563:Membrane Lipids; D010714:Phosphatidylethanolamines; D011943:Receptors, Adrenergic, beta; D008780:Methyltransferases; D050918:Phosphatidylethanolamine N-Methyltransferase; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D000262:Adenylyl Cyclases