An alternative splicing form of phosphatidylserine-specific phospholipase A₁ that exhibits lysophosphatidylserine-specific lysophospholipase activity in humans

Phosphatidylserine-specific phospholipase A₁ (PS-PLA₁), which acts specifically on phosphatidylserine (PS) and 1-acyl-2-lysophosphatidylserine (lyso-PS) to hydrolyze fatty acids at the sn-1 position of these phospholipids, was first identified in rat platelets (Sato, T., Aoki, J., Nagai, Y., Dohmae, 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 encoding human PS-PLA₁, which showed 80% homology with rat PS-PLA₁ at the amino acid level. In addition to an mRNA encoding a 456-amino acid product (PS-PLA₁), an mRNA with four extra bases inserted at the boundary of the exon-intron junction was detected in human tissues and various human cell lines. This mRNA is most probably produced via an alternative use of the 5'- splicing site (two consensus sequences for RNA splicing occur at the boundary of the exon-intron junction) and encodes a 376-amino acid product (PS- PLA₁ΔC) that lacks two-thirds of the C-terminal domain of PS-PLA₁. Unlike PS-PLA₁, PS-PLA₁ΔC hydrolyzed exclusively lyso-PS but not PS appreciably. Any other phospholipids such as phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidic acid (PA), and their lyso derivatives were not hydrolyzed at all. These data demonstrated that PS- PLA₁ΔC exhibits lyso-PS-specific lysophospholipase activity and that the C- terminal domain of PS-PLA₁ is responsible for recognizing diacylphospholipids. In addition, human PS-PLA₁ gene was mapped to chromosome 3q13.13-13.2 and was unexpectedly identical to the nmd gene, which is highly expressed in nonmetastatic melanoma cell lines but poorly expressed in metastatic cell lines (van Groningen, J. J., Bloemers, H. P., and Swart, G. W. (1995) Cancer Res. 55, 6237-6243).