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.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medicinal Chemistry (hsv//eng)

Keyword

Research Support

Recombinant Proteins/metabolism

Prostate-Specific Antigen/*metabolism

Kallikreins/*metabolism

Humans

Enzyme Activation

Enzyme Precursors/*metabolism

Non-U.S. Gov't

Substrate Specificity

Tissue Kallikreins

Publication and Content Type

art (subject category)

ref (subject category)