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Blood First Edition Paper, prepublished online November 6, 2009; DOI 10.1182/blood-2008-11-188938. This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted 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 CrossRef Google Scholar Articles by Andronicos, N. M. Articles by Miles, L. A. PubMed PubMed Citation Articles by Andronicos, N. M. Articles by Miles, L. A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 13, 2008; accepted October 9, 2009. Proteomics-based discovery of a novel, structurally unique, and developmentally regulated plasminogen receptor, Plg-RKT, a major regulator of cell surface plasminogen activation Nicholas M. Andronicos1, Emily I. Chen1, Nagyung Baik1, Hongdong Bai1, Caitlin M. Parmer1, William B. Kiosses1, Mark P. Kamps2, John R. Yates, III1, Robert J. Parmer3 and Lindsey A. Miles1,3 1 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA, United States; 2 Department of Pathology, University of California San Diego, La Jolla, CA, United States; 3 Department of Medicine, University of California San Diego, La Jolla, CA, United States * Corresponding author; email: lmiles{at}scripps.edu Abstract Activation of plasminogen, the zymogen of the primary thrombolytic enzyme, plasmin, is markedly promoted when plasminogen is bound to cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin. In addition to its role in thrombolysis, cell surface plasmin facilitates a wide array of physiological and pathological processes. Carboxypeptidase B-sensitive plasminogen binding sites promote plasminogen activation on eukaryotic cells. However, no integral membrane plasminogen receptors exposing carboxyl terminal basic residues on cell surfaces have been identified. Here we utilize the exquisite sensitivity of multidimensional protein identification technology and an inducible progenitor cell line to identify a novel differentiation-induced integral membrane plasminogen receptor that exposes a C-terminal lysine on the cell surface, Plg-RKT (C9orf46 homolog). Plg-RKT was highly co-localized on the cell surface with the urokinase receptor, uPAR. Our data suggest that Plg-RKT also interacts directly with tissue plasminogen activator. Furthermore, Plg-RKT markedly promoted cell surface plasminogen activation. Database searching revealed that Plg-RKT mRNA is broadly expressed by migratory cell types, including leukocytes, breast cancer, leukemic and neuronal cells. This structurally unique plasminogen receptor, represents a novel control point for regulating cell surface proteolysis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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