title: The plasminogen receptor, Plg-R(KT), and macrophage function.
abstract: When plasminogen binds to cells its activation to plasmin is markedly enhanced compared to the reaction in solution. Thus, cells become armed with the broad spectrum proteolytic activity of plasmin. Cell-surface plasmin plays a key role in macrophage recruitment during the inflammatory response. Proteins exposing basic residues on the cell surface promote plasminogen activation on eukaryotic cells. We have used a proteomics approach combining targeted proteolysis with carboxypeptidase B and multidimensional protein identification technology, MudPIT, and a monocyte progenitor cell line to identify a novel transmembrane protein, the plasminogen receptor, Plg-R(KT). Plg-R(KT) exposes a C-terminal lysine on the cell surface in an orientation to bind plasminogen and promote plasminogen activation. Here we review the characteristics of this new protein, with regard to membrane topology, conservation of sequence across species, the role of its C-terminus in plasminogen binding, its function in plasminogen activation, cell migration, and its role in macrophage recruitment in the inflammatory response.
authors.affiliation: Department of Cell Biology, The Scripps Research Institute, 10550 N. Torrey Pines Road, SP30-3020, La Jolla, CA 92037, USA.
authors.forename: Lindsey A
authors.initials: LA
authors.lastname: Miles
authors.forename: Shahrzad
authors.initials: S
authors.lastname: Lighvani
authors.forename: Nagyung
authors.initials: N
authors.lastname: Baik
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Andronicos
authors.forename: Emily I
authors.initials: EI
authors.lastname: Chen
authors.forename: Caitlin M
authors.initials: CM
authors.lastname: Parmer
authors.forename: Sophia
authors.initials: S
authors.lastname: Khaldoyanidi
authors.forename: Jenna E
authors.initials: JE
authors.lastname: Diggs
authors.forename: William B
authors.initials: WB
authors.lastname: Kiosses
authors.forename: Mark P
authors.initials: MP
authors.lastname: Kamps
authors.forename: John R
authors.initials: JR
authors.lastname: Yates
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Parmer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017124:Conserved Sequence; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D008239:Lysine / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008969:Molecular Sequence Data; D010958:Plasminogen / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D008239:Lysine