HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 280, Issue 15, 14628-14635, April 15, 2005

This Article Full Text Full Text (PDF) All Versions of this Article: 280/15/14628    most recent M408132200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Michael, I. P. Articles by Diamandis, E. P. Search for Related Content PubMed PubMed Citation Articles by Michael, I. P. Articles by Diamandis, E. P. Social Bookmarking                      What's this?

Biochemical and Enzymatic Characterization of Human Kallikrein 5 (hK5), a Novel Serine Protease Potentially Involved in Cancer Progression^*

Iacovos P. Michael, Georgia Sotiropoulou¶, Georgios Pampalakis¶, Angeliki Magklara, Manik Ghosh, Greg Wasney, and Eleftherios P. Diamandis||

From the Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada, the Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L5, Canada, and the ^¶Department of Pharmacy, School of Health Sciences, University of Patras, Rion, 26500 Patra, Greece

Human kallikrein 5 (KLK5) is a member of the human kallikrein gene family of serine proteases. Preliminary results indicate that the protein, hK5, may be a potential serological marker for breast and ovarian cancer. Other studies implicate hK5 with skin desquamation and skin diseases. To gain further insights on hK5 physiological functions, we studied its substrate specificity, the regulation of its activity by various inhibitors, and identified candidate physiological substrates. After producing and purifying recombinant hK5 in yeast, we determined the k_cat/K_m ratio of the fluorogenic substrates Gly-Pro-Arg-AMC and Gly-Pro-Lys-AMC, and showed that it has trypsin-like activity with strong preference for Arg over Lys in the P1 position. The serpins ₂-antiplasmin and antithrombin were able to inhibit hK5 with an inhibition constant (k₊₂/K_i) of 1.0 x 10^{– 2}and 4.2 x 10^–4 M^–1 min^–1, respectively. No inhibition was observed with the serpins ₁-antitrypsin and ₁-antichymotrypsin, although ₂-macroglobulin partially inhibited hK5 at high concentrations. We also demonstrated that hK5 can efficiently digest the extracellular matrix components, collagens type I, II, III, and IV, fibronectin, and laminin. Furthermore, our results suggest that hK5 can potentially release (a) angiostatin 4.5 from plasminogen, (b) "cystatin-like domain 3" from low molecular weight kininogen, and (c) fibrinopeptide B and peptide 15-42 from the B chain of fibrinogen. hK5 could also play a role in the regulation of the binding of plasminogen activator inhibitor 1 to vitronectin. Our findings suggest that hK5 may be implicated in tumor progression, particularly in invasion and angiogenesis, and may represent a novel therapeutic target.

Received for publication, July 19, 2004 , and in revised form, January 27, 2005.

^* This work was supported by a University-Industry Grant from the Natural Sciences and Engineering Research Council of Canada and IBEX Technologies (to E. P. D.) and Hellenic General Secretariat of Research and Technology and European Union, through research project PENED 2001 (01ED557) of Operational Program Competitiveness (to G. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^|| To whom correspondence should be addressed: Dept. of Pathology and Laboratory Medicine, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario M5G 1X5, Canada. Tel.: 416-586-8443; Fax: 416-586-8628; E-mail: ediamandis{at}mtsinai.on.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				N. Emami, D. Deperthes, J. Malm, and E. P. Diamandis Major Role of Human KLK14 in Seminal Clot Liquefaction J. Biol. Chem., July 11, 2008; 283(28): 19561 - 19569. [Abstract] [Full Text] [PDF]

				H. Yoon, G. Laxmikanthan, J. Lee, S. I. Blaber, A. Rodriguez, J. M. Kogot, I. A. Scarisbrick, and M. Blaber Activation Profiles and Regulatory Cascades of the Human Kallikrein-related Peptidases J. Biol. Chem., November 2, 2007; 282(44): 31852 - 31864. [Abstract] [Full Text] [PDF]

				C. A. Borgono, I. P. Michael, N. Komatsu, A. Jayakumar, R. Kapadia, G. L. Clayman, G. Sotiropoulou, and E. P. Diamandis A Potential Role for Multiple Tissue Kallikrein Serine Proteases in Epidermal Desquamation J. Biol. Chem., February 9, 2007; 282(6): 3640 - 3652. [Abstract] [Full Text] [PDF]

				C. A. Borgono, I. P. Michael, J. L. V. Shaw, L.-Y. Luo, M. C. Ghosh, A. Soosaipillai, L. Grass, D. Katsaros, and E. P. Diamandis Expression and Functional Characterization of the Cancer-related Serine Protease, Human Tissue Kallikrein 14 J. Biol. Chem., January 26, 2007; 282(4): 2405 - 2422. [Abstract] [Full Text] [PDF]

				K. Oikonomopoulou, K. K. Hansen, M. Saifeddine, I. Tea, M. Blaber, S. I. Blaber, I. Scarisbrick, P. Andrade-Gordon, G. S. Cottrell, N. W. Bunnett, et al. Proteinase-activated Receptors, Targets for Kallikrein Signaling J. Biol. Chem., October 27, 2006; 281(43): 32095 - 32112. [Abstract] [Full Text] [PDF]

				K. Yamasaki, J. Schauber, A. Coda, H. Lin, R. A. Dorschner, N. M. Schechter, C. Bonnart, P. Descargues, A. Hovnanian, and R. L. Gallo Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin FASEB J, October 1, 2006; 20(12): 2068 - 2080. [Abstract] [Full Text] [PDF]

				M. Debela, V. Magdolen, N. Schechter, M. Valachova, F. Lottspeich, C. S. Craik, Y. Choe, W. Bode, and P. Goettig Specificity Profiling of Seven Human Tissue Kallikreins Reveals Individual Subsite Preferences J. Biol. Chem., September 1, 2006; 281(35): 25678 - 25688. [Abstract] [Full Text] [PDF]

				M. H. Slagter, L. J.G. Gooren, W. de Ronde, A. Soosaipillai, A. Scorilas, E. J. Giltay, M. Paliouras, and E. P. Diamandis Serum and Urine Tissue Kallikrein Concentrations in Male-to-Female Transsexuals Treated with Antiandrogens and Estrogens Clin. Chem., July 1, 2006; 52(7): 1356 - 1365. [Abstract] [Full Text] [PDF]

				I. P. Michael, G. Pampalakis, S. D. Mikolajczyk, J. Malm, G. Sotiropoulou, and E. P. Diamandis Human Tissue Kallikrein 5 Is a Member of a Proteolytic Cascade Pathway Involved in Seminal Clot Liquefaction and Potentially in Prostate Cancer Progression J. Biol. Chem., May 5, 2006; 281(18): 12743 - 12750. [Abstract] [Full Text] [PDF]

				L.-Y. Luo, S. J.C. Shan, M. B. Elliott, A. Soosaipillai, and E. P. Diamandis Purification and Characterization of Human Kallikrein 11, a Candidate Prostate and Ovarian Cancer Biomarker, from Seminal Plasma Clin. Cancer Res., February 1, 2006; 12(3): 742 - 750. [Abstract] [Full Text] [PDF]

				N. L.G. Sieben, J. Oosting, A. M. Flanagan, J. Prat, G. M.J.M. Roemen, S. M. Kolkman-Uljee, R. van Eijk, C. J. Cornelisse, G. J. Fleuren, and M. van Engeland Differential Gene Expression in Ovarian Tumors Reveals Dusp 4 and Serpina 5 As Key Regulators for Benign Behavior of Serous Borderline Tumors J. Clin. Oncol., October 10, 2005; 23(29): 7257 - 7264. [Abstract] [Full Text] [PDF]