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Blood, 15 February 2006, Vol. 107, No. 4, pp. 1397-1404. Prepublished online as a Blood First Edition Paper on October 13, 2005; DOI 10.1182/blood-2005-08-3452. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3452v1 107/4/1397    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 Lee, K. N. Articles by McKee, P. A. Search for Related Content PubMed PubMed Citation Articles by Lee, K. N. Articles by McKee, P. A. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Free Research Articles Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Antiplasmin-cleaving enzyme is a soluble form of fibroblast activation protein Kyung N. Lee, Kenneth W. Jackson, Victoria J. Christiansen, Chung S. Lee, Jin-Geun Chun, and Patrick A. McKee From the William K. Warren Medical Research Center and Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK. Circulating antiplasmin-cleaving enzyme (APCE) has a role in fibrinolysis and appears structurally similar to fibroblast activation protein (FAP), a cell-surface proteinase that promotes invasiveness of certain epithelial cancers. To explore this potential relationship, we performed comparative structure/function analyses of the 2 enzymes. APCE from human plasma and recombinant FAP (rFAP) exhibited identical pH optima of 7.5, extinction coefficients () of 20.2 and 20.5, common sequences of tryptic peptides, and cross-reactivity with FAP antibody. APCE and rFAP are homodimers with monomeric subunits of 97 and 93 kDa. Only homodimers appear to have enzymatic activity, with essentially identical kinetics toward Met-2-antiplasmin (Met-2AP) and peptide substrates. APCE and rFAP cleave both Pro3-Leu4 and Pro12-Asn13 bonds of Met-2AP, but relative kcat/Km values for Pro12-Asn13 are about 16-fold higher than for Pro3-Leu4. APCE and rFAP demonstrate higher kcat/Km values toward a peptide modeled on P4-P4' sequence surrounding the Pro12-Asn13 primary cleavage site than for Z-Gly-Pro-AMC and Ala-Pro-AFC substrates. These data support APCE as a soluble derivative of FAP and Met-2AP as its physiologic substrate. Conversion of Met-2AP by membrane or soluble FAP to the more easily fibrin-incorporable form, Asn-2AP, may increase plasmin inhibition within fibrin surrounding certain neoplasms and have an impact on growth and therapeutic susceptibility. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: E. Ostermann, P. Garin-Chesa, K. H. Heider, M. Kalat, H. Lamche, C. Puri, D. Kerjaschki, W. J. Rettig, and G. R. Adolf Effective Immunoconjugate Therapy in Cancer Models Targeting a Serine Protease of Tumor Fibroblasts Clin. Cancer Res., July 15, 2008; 14(14): 4584 - 4592. [Abstract] [Full Text] [PDF] V. J. Christiansen, K. W. Jackson, K. N. Lee, and P. A. McKee The effect of a single nucleotide polymorphism on human {alpha}2-antiplasmin activity Blood, June 15, 2007; 109(12): 5286 - 5292. [Abstract] [Full Text] [PDF] H.-J. Lee, Y.-S. Chen, C.-Y. Chou, C.-H. Chien, C.-H. Lin, G.-G. Chang, and X. Chen Investigation of the Dimer Interface and Substrate Specificity of Prolyl Dipeptidase DPP8 J. Biol. Chem., December 15, 2006; 281(50): 38653 - 38662. [Abstract] [Full Text] [PDF]

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