An alternative splicing form of phosphatidylserine-specific phospholipase A(1) that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans

Phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)), which acts spec ifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (ly so-PS) to hydrolyze fatty acids at the sn-l position of these phospholipids , was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Doh mae, N., Takio, K., Doi, T., Arai, H., and Inoue, K. (1997) J. Biol. Chem. 272, 2192-2198). In this study we isolated and sequenced cDNA clones encodi ng human PS-PLA(1), which showed 80% homology with rat PS-PLA(1) at the ami no acid level. In addition to an mRNA encoding a 456-amino acid product (PS -PLA(1)), an mRNA with four extra bases inserted at the boundary of the exo n-intron junction was detected in human tissues and various human cell line s. This mRNA is most probably produced via an alternative use of the 5'-spl icing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS-PLA(1 )Delta C) that lacks two-thirds of the C-terminal domain of PS PLA(1). Unli ke PS-PLA(1), PS-PLA(1)Delta C hydrolyzed exclusively lyso-PS but not PS ap preciably. Any other phospholipids such as phosphatidylcholine (PC), phosph atidylethanolamine (PE), phosphatidic acid (PA), and their lyse derivatives were not hydrolyzed at all. These data demonstrated that PS-PLA(1)Delta C exhibits lyso-PS-specific lysophospholipase activity and that the C-termina l domain of PS-PLA(1) is responsible for recognizing diacylphospholipids. I n addition, human PS-PLA(1) gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in no nmetastatic melanoma cell lines but poorly expressed in metastatic cell lin es (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer R es. 55, 6237-6243).