Rabbit procathepsin E and cathepsin E

Nucleotide sequence of cDNA, hydrolytic specificity for biologically active peptides and gene expression during development

The structure of rabbit procathepsin E was determined by molecular cloning of its cDNA. The proenzyme consisted of 379 amino acids and had structural features common to human and guineapig procathepsin E species. The highly conserved tripeptide sequence at the active site of aspartic proteinases, Asp-Thr(Ser)-Gly, is, however, replaced by Asp-Thr-Val in rabbit procathepsin E. To our knowledge, this is the first case of such a variation in aspartic proteinases. The processed form, cathepsin E, hydrolyzed various biologically active peptides maximally at around pH 5 Tachykinins, such as substance P and neurokinin A, were hydrolyzed most rapidly, with specific cleavge of sequences essential for their activity. The rates of hydrolysis were several hundred-fold higher than those of cathepsin D. Furthermore, cathepsin E was able to inactivate a functional-domain peptide of fibroblast growth factor, the sequence of which resembles those of tachykinins, and it was active in the generation of functional peptides, such as endothelin and angiotensin I, from their respective precursors. Procathepsin E was detected at high levels in various fetal tissues, such as the liver, stomach and blood cells. At the adult stage, the proenzyme was detectable only in specific tissues, such as the urinary bladder, duodenum and colon. Northern-blot analysis showed similar stage-specific and tissue-specific expression of the mRNA for procathepsin E. Since tachykinins and other suited peptide substrates of cathepsin E have been shown to have mitogenic activity, (pro)cathepsin E may regulate the growth and differention of embryonic and fetal tissues by degrading or processing these peptides. The enzyme may also regulate the physiological activities of adult tissues which are mediated by substance P and related tachykinins.