MOLECULAR-CLONING AND EXPRESSION OF PALMITOYL-PROTEIN THIOESTERASE-2 (PPT2), A HOMOLOG OF LYSOSOMAL PALMITOYL-PROTEIN THIOESTERASE WITH A DISTINCT SUBSTRATE-SPECIFICITY

Palmitoyl-protein thioesterase is a lysosomal hydrolase that, removes long chain fatty acyl groups from modified cysteine residues in protei ns, Mutations in this enzyme were recently shown to underlie the hered itary neurodegenerative disorder, infantile neuronal ceroid lipofuscin osis, and lipid thioesters derived from acylated proteins were found t o accumulate in lymphoblasts from individuals with the disorder. In th e current study, we describe the cloning and expression of a second ly sosomal thioesterase, palmitoyl-protein thioesterase 2 (PPT2), that sh ares an 18% identity with palmitoyl-protein thioesterase, Transient ex pression of a PPT2 cDNA led to the production of a glycosylated lysoso mal protein with palmitoyl-CoA hydrolase activity comparable with palm itoyl-protein thioesterase, However, PPT2 did not remove palmitate gro ups from palmitoylated proteins that are substrates for palmitoyl-prot ein thioesterase, In cross-correction experiments, PPT2 did not abolis h the accumulation of protein-derived lipid thioesters in palmitoyl-pr otein thioesterase-deficient cell lines, These results indicate that P PT2 is a lysosomal thioesterase that possesses a substrate specificity that is distinct from that of palmitoyl-protein thioesterase.