Vesicular localization and characterization of a novel post-proline-cleaving aminodipeptidase, quiescent cell proline dipeptidase

A large number of chemokines, cytokines, and signal peptides share a highly conserved X-Pro motif on the N-terminus, The cleavage of this N-terminal X -Pro dipeptide results in functional alterations of chemokines such as RANT ES, stroma-derived factor-1, and macrophage-derived chemokine, Until recent ly, CD26/DPPIV was the only known protease with the ability to cleave N-ter minal X-Pro motifs at neutral pH, We have isolated and cloned a novel serin e protease, quiescent cell proline dipeptidase (QPP), with substrate specif icity similar to that of CD26/DPPIV, In this paper we show that QPP, like C D26/DPPIV, is synthesized with a propeptide and undergoes N-glycosylation, Interestingly, this glycosylation is required for QPP enzymatic activity, b ut not for its localization, Unlike the cell surface molecule, CD26/DPPIV, QPP is targeted to intracellular vesicles that are distinct from lysosomes, Proteinase K treatment of intact vesicles indicates that QPP is located wi thin the vesicles, These vesicles appear to have a secretory component, as QPP is secreted in a functionally active form in response to calcium releas e. The presence of QPP in the vesicular compartment. suggests that molecule s bearing the N-terminal X-Pro motif can be cleaved at multiple sites withi n and outside the cell, These results expand the potential site(s) and scop e of a process that appears to be an important mechanism of post-translatio nal regulation.