New members of the mammalian glycerophosphodiester phosphodiesterase family: GDE4 and GDE7 produce lysophosphatidic acid by lysophospholipase D activity [Signal Transduction]

December 20th, 2014 by Ohshima, N., Kudo, T., Yamashita, Y., Mariggio, S., Araki, M., Honda, A., Nagano, T., Isaȷi, C., Kato, N., Corda, D., Izumi, T., Yanaka, N.

The known mammalian glycerophosphodiester phosphodiesterases (GP-PDEs) hydrolyze glycerophosphodiesters. In this study, two novel members of the mammalian GP-PDE family, GDE4 and GDE7, were isolated and the molecular basis of mammalian GP-PDEs was further explored. The GDE4 and GDE7 sequences are highly homologous and evolutionarily close. GDE4 is expressed in intestinal epithelial cells, spermatids and macrophages, whereas GDE7 is particularly expressed in gastro-esophageal epithelial cells. Unlike other mammalian GP-PDEs, GDE4 and GDE7 cannot hydrolyze either glycerophosphoinositol or glycerophosphocholine. Unexpectedly, both GDE4 and GDE7 show a lysophospholipase D activity towards lysophosphatidylcholine (lysoPC). We purified the recombinant GDE4 and GDE7 proteins and show that these enzymes can hydrolyze lysoPC, to produce lysophosphatidic acid (LPA). Further characterization of purified recombinant GDE4 showed that it can also convert lyso-platelet-activating factor (1-O-alkyl-sn-glycero-3-phosphocholine; lyso-PAF) to alkyl-LPA. These data contribute to our current understanding of mammalian GP-PDEs and of their physiological roles via the control of lysoPC and lyso-PAF metabolism in gastro-intestinal epithelial cells and activated macrophages.
  • Posted in Journal of Biological Chemistry, Publications
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