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Journal of Clinical Endocrinology & Metabolism, Vol 75, 1046-1053, Copyright © 1992 by Endocrine Society

ARTICLES

Prostate-specific antigen (PSA) is an insulin-like growth factor binding protein-3 protease found in seminal plasma

P Cohen, HC Graves, DM Peehl, M Kamarei, LC Giudice and RG Rosenfeld
Department of Pediatrics, Stanford University Medical Center, California 94305.

Insulin-like growth factor binding protein-3 (IGFBP-3), the major serum carrier protein for the IGFs, is absent from Western ligand blots of seminal plasma, but is detectable by RIA. IGFBP-3 protease activity has recently been described in pregnancy serum. We investigated the possibility that seminal plasma contains an IGFBP-3 protease, by incubating seminal plasma with 125I-labeled human IGFBP-3. Seminal plasma was found to have potent IGFBP-3 protease activity with a cleavage pattern different from that of pregnancy serum. Prostate- specific antigen (PSA) is a serine protease found in semen. Autoradiographs measuring IGFBP-3 protease activity demonstrated that purified PSA cleaved IGFBP-3, yielding a cleavage pattern identical to that of seminal plasma. IGFBP-2 and -4 in seminal plasma were not degraded by PSA. Cleavage of IGFBP-3 by PSA resulted in a marked reduction in the binding affinity of the fragments to IGF-I, but not IGF-II. We speculate that PSA may serve to modulate IGF function within the reproductive system or in prostate cancer by altering IGF-IGFBP-3 interactions.


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J. Clin. Endocrinol. Metab., July 1, 1997; 82(7): 2198 - 2203.
[Abstract] [Full Text] [PDF]

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S. Xu, P. Savage, J. L. Burton, J. Sansom, and J. M. P. Holly
Proteolysis of Insulin-Like Growth Factor-Binding Protein-3 by Human Skin Keratinocytes in Culture in Comparison to that in Skin Interstitial Fluid: The Role and Regulation of Components of the Plasmin System
J. Clin. Endocrinol. Metab., June 1, 1997; 82(6): 1863 - 1868.
[Abstract] [Full Text] [PDF]

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J. L. Fowlkes, K. M. Thrailkill, C. George-Nascimento, C. K. Rosenberg, and D. M. Serra
Heparin-Binding, Highly Basic Regions within the Thyroglobulin Type-1 Repeat of Insulin-Like Growth Factor (IGF)-Binding Proteins (IGFBPs) -3, -5, and -6 Inhibit IGFBP-4 Degradation
Endocrinology, June 1, 1997; 138(6): 2280 - 2285.
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H. Salahifar, R. C. Baxter, and J. L. Martin
Insulin-like Growth Factor Binding Protein (IGFBP)-3 Protease Activity Secreted by MCF-7 Breast Cancer Cells: Inhibition by IGFs Does Not Require IGF-IGFBP Interaction
Endocrinology, April 1, 1997; 138(4): 1683 - 1690.
[Abstract] [Full Text] [PDF]

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 Clin. Chem.Home page
A. Herrala, R. Kurkela, K. Porvari, R. Isomaki, P. Henttu, and P. Vihko
Human prostate-specific glandular kallikrein is expressed as an active and an inactive protein
Clin. Chem., February 1, 1997; 43(2): 279 - 284.
[Abstract] [Full Text] [PDF]

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H. Yu, E. P. Diamandis, M. Monne, and C. M. Croce
Oral Contraceptive-induced Expression of Prostate-specific Antigen in the Female Breast
J. Biol. Chem., March 24, 1995; 270(12): 6615 - 6618.
[Abstract] [Full Text] [PDF]

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T. J. Harvey, J. D. Hooper, S. A. Myers, S.-A. Stephenson, L. K. Ashworth, and J. A. Clements
Tissue-specific Expression Patterns and Fine Mapping of the Human Kallikrein (KLK) Locus on Proximal 19q13.4
J. Biol. Chem., November 22, 2000; 275(48): 37397 - 37406.
[Abstract] [Full Text] [PDF]


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