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Blood, 15 October 2006, Vol. 108, No. 8, pp. 2616-2623. Prepublished online as a Blood First Edition Paper on June 22, 2006; DOI 10.1182/blood-2006-02-001073. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-02-001073v1 108/8/2616    most recent Alert me when this article is cited 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Kilpatrick, L. M. Articles by Ellis, V. Search for Related Content PubMed PubMed Citation Articles by Kilpatrick, L. M. Articles by Ellis, V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Initiation of plasminogen activation on the surface of monocytes expressing the type II transmembrane serine protease matriptase Lynette M. Kilpatrick, Roger L. Harris, Kate A. Owen, Rosemary Bass, Christine Ghorayeb, Amit Bar-Or, and Vincent Ellis From the School of Biological Sciences, University of East Anglia, Norwich, United Kingdom; and Montreal Neurological Institute, McGill University, Montreal, QC, Canada. uPA (urokinase-type plasminogen activator) activates plasminogen with high efficiency when bound to its cellular receptor uPAR, but only after a prolonged lag phase during which generated plasmin activates pro-uPA. How the activity of this proteolytic system might be rapidly initiated is unknown. We have now found that 2 monocytic cell lines display distinct patterns of plasminogen activation. U937 cells, but not THP-1 cells, displayed the expected lag phase, suggesting a constitutive initiation mechanism on the latter. This was shown to be due to the plasmin-independent activation of uPAR-bound pro-uPA by a cell surface-associated protease and to correlate with the expression of matriptase, a type II transmembrane serine protease that was highly expressed in THP-1 cells but undetectable in U937 cells. Kinetic analysis demonstrated that matriptase is a relatively poor activator of pro-uPA in solution, approximately 100-fold less efficient than plasmin (kcat/Km 1.16 x 105 M-1s-1 cf 1.21 x 107 M-1s-1). However, down-regulation of matriptase expression in THP-1 cells by siRNA reduced the activation of cell-associated pro-uPA and the subsequent rapid initiation of plasminogen activation by 76% to 93%. Matriptase was also found to be expressed by peripheral blood monocytes and may therefore be a specific mechanism for the rapid initiation and regulation of plasminogen activation by these cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. H. Bugge, T. M. Antalis, and Q. Wu Type II Transmembrane Serine Proteases J. Biol. Chem., August 28, 2009; 284(35): 23177 - 23181. [Abstract] [Full Text] [PDF] R. Szabo, J. P. Hobson, K. Christoph, P. Kosa, K. List, and T. H. Bugge Regulation of cell surface protease matriptase by HAI2 is essential for placental development, neural tube closure and embryonic survival in mice Development, August 1, 2009; 136(15): 2653 - 2663. [Abstract] [Full Text] [PDF] R. Szabo, P. Kosa, K. List, and T. H. Bugge Loss of Matriptase Suppression Underlies Spint1 Mutation-Associated Ichthyosis and Postnatal Lethality Am. J. Pathol., June 1, 2009; 174(6): 2015 - 2022. [Abstract] [Full Text] [PDF] G. E. Blouse, K. A. Botkjaer, E. Deryugina, A. A. Byszuk, J. M. Jensen, K. K. Mortensen, J. P. Quigley, and P. A. Andreasen A Novel Mode of Intervention with Serine Protease Activity: TARGETING ZYMOGEN ACTIVATION J. Biol. Chem., February 13, 2009; 284(7): 4647 - 4657. [Abstract] [Full Text] [PDF] R. Szabo, J. P. Hobson, K. List, A. Molinolo, C.-Y. Lin, and T. H. Bugge Potent Inhibition and Global Co-localization Implicate the Transmembrane Kunitz-type Serine Protease Inhibitor Hepatocyte Growth Factor Activator Inhibitor-2 in the Regulation of Epithelial Matriptase Activity J. Biol. Chem., October 24, 2008; 283(43): 29495 - 29504. [Abstract] [Full Text] [PDF] A. P. Mazar Urokinase Plasminogen Activator Receptor Choreographs Multiple Ligand Interactions: Implications for Tumor Progression and Therapy Clin. Cancer Res., September 15, 2008; 14(18): 5649 - 5655. [Abstract] [Full Text] [PDF] I-C. Tseng, F.-P. Chou, S.-F. Su, M. Oberst, N. Madayiputhiya, M.-S. Lee, J.-K. Wang, D. E. Sloane, M. Johnson, and C.-Y. Lin Purification from human milk of matriptase complexes with secreted serpins: mechanism for inhibition of matriptase other than HAI-1 Am J Physiol Cell Physiol, August 1, 2008; 295(2): C423 - C431. [Abstract] [Full Text] [PDF] P. Ghosh, M. Garcia-Marcos, S. J. Bornheimer, and M. G. Farquhar Activation of G{alpha}i3 triggers cell migration via regulation of GIV J. Cell Biol., July 28, 2008; 182(2): 381 - 393. [Abstract] [Full Text] [PDF] K. List, B. Currie, T. C. Scharschmidt, R. Szabo, J. Shireman, A. Molinolo, B. F. Cravatt, J. Segre, and T. H. Bugge Autosomal Ichthyosis with Hypotrichosis Syndrome Displays Low Matriptase Proteolytic Activity and Is Phenocopied in ST14 Hypomorphic Mice J. Biol. Chem., December 14, 2007; 282(50): 36714 - 36723. [Abstract] [Full Text] [PDF]

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