title: Prostate-specific antigen activates single-chain urokinase-type plasminogen activator.
abstract: Prostate-specific antigen (PSA) increases in the plasma of patients with prostate cancer, and has therefore been used as a reliable tumor marker. It has been demonstrated that prostate cancer cells over-express urokinase-type plasminogen activator (uPA), which plays an important role in tumor invasion and metastasis. We found that PSA converts the single-chain proform of urokinase-type plasminogen activator (scuPA) to an active 2-chain form. The active 2-chain uPA generated from scuPA by PSA was measured by hydrolyzation of S-2444, a synthetic substrate for uPA. PSA activated scuPA time- and dose-dependently. SDS-PAGE analysis revealed that, after incubation with PSA, the intensity of the 55-kDa band of scuPA decreased concomitantly with increases in the intensity of the 2 bands at 33 kDa and 22 kDa. Amino-acid-sequence analysis indicated that PSA cleaved Lys158-Ile159, which corresponds with the site cleaved by plasmin. PSA did not enhance or impair the activity of the 2-chain form of uPA. These findings imply that PSA could be an initiator of the protease cascade involved in prostate-cancer invasion and metastasis.
authors.affiliation: Department of Physiology, Miyazaki Medical College, Japan.
authors.forename: E
authors.initials: E
authors.lastname: Yoshida
authors.forename: S
authors.initials: S
authors.lastname: Ohmura
authors.forename: M
authors.initials: M
authors.lastname: Sugiki
authors.forename: M
authors.initials: M
authors.lastname: Maruyama
authors.forename: H
authors.initials: H
authors.lastname: Mihara
mesh_terms: D000595:Amino Acid Sequence; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism*
chemical_list: D014568:Urokinase-Type Plasminogen Activator; D017430:Prostate-Specific Antigen