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 enzymes are synthesized with a propeptide that is supposedly cleaved off in the prostate to yield the mature forms found in semen. We have purified and characterised recombinant PSA and hK2 produced in eucaryotic cells. Recombinant PSA was recovered as a zymogen and recombinant hK2 was 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 substrate; the hK2-proPSA ratio used was similar to the enzyme-substrate ratio that prevails under phyciological conditions. Our results indicate that hK2 is responsible for the activation of proPSA, a finding that may be very important for understanding of the role of these two kallikreins in the reproductive system and in prostate cancer biology.
Lövgren
J
J
Department of Clinical Chemistry, Lund University Hospital, Malmö, S-205 02, Sweden. janita.lovgren@utu.fi
Rajakoski
K
K
Karp
M
M
Lundwall â
Lilja
H
H
D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D006801:Humans; D007610:Kallikreins / Q000378:metabolism*; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D013379:Substrate Specificity; D020840:Tissue Kallikreins
D004792:Enzyme Precursors; D011994:Recombinant Proteins; D007610:Kallikreins; D020840:Tissue Kallikreins; D017430:Prostate-Specific Antigen