ACTIVATION OF THE ZYMOGEN FORM OF PROSTATE-SPECIFIC ANTIGEN BY HUMAN GLANDULAR KALLIKREIN-2

Prostate-specific antigen (PSA) and human glandular kallikrein 2 (hK2) are glandular kallikreins secreted by the prostate gland. Both enzyme s are synthesized with a propeptide that is supposedly cleaved off in the prostate to yield the mature forms found in semen. We have purifie d and characterised recombinant PSA and hK2 produced in eucaryotic cel ls. Recornbinant PSA was recovered as a zymogen and recombinant hK2 wa s recovered in mature form. The zymogen form of PSA had no or very low enzymatic activity. After incubation with hK2, proPSA was activated, as shown by the cleavage of the seminal gel proteins and a peptide sub strate; the hK2-proPSA ratio used was similar to the enzyme-substrate ratio that prevails under phyciological conditions. Our results indica te that hK2 is responsible for the activation of proPSA, a finding tha t may be very important for understanding of the role of these two kal likreins in the reproductive system and in prostate cancer biology. (C ) 1997 Academic Press.