title: Plasminogen is tethered with high affinity to the cell surface by the plasma protein, histidine-rich glycoprotein.
abstract: Plasminogen has been implicated in extracellular matrix degradation by invading cells, but few high affinity cell surface receptors for the molecule have been identified. Previous studies have reported that the plasma protein, histidine-rich glycoprotein (HRG), interacts with plasminogen and cell surfaces, raising the possibility that HRG may immobilize plasminogen/plasmin to cell surfaces. Here we show, based on optical biosensor analyses, that immobilized HRG interacts with soluble plasminogen with high affinity and with an extremely slow dissociation rate. Furthermore, the HRG-plasminogen interaction is lysine-dissociable and involves predominately the amino-terminal domain of HRG, and the fifth kringle domain of plasminogen, but not the carboxyl-terminal lysine of HRG. HRG was also shown to tether plasminogen to cell surfaces, with this interaction being potentiated by elevated Zn(2+) levels and low pH, conditions that prevail at sites of tissue injury, tumor growth, and angiogenesis. Based on these data we propose that HRG acts as a soluble adaptor molecule that binds to cells at sites of tissue injury, tumor growth, and angiogenesis, providing a high affinity receptor for tethering plasminogen to the cell surface and thereby enhancing the migratory potential of cells.
authors.affiliation: Cancer and Vascular Biology Group, Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory 2601, Australia.
authors.forename: Allison L
authors.initials: AL
authors.lastname: Jones
authors.forename: Mark D
authors.initials: MD
authors.lastname: Hulett
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Altin
authors.forename: Phillip
authors.initials: P
authors.lastname: Hogg
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Parish
mesh_terms: D043168:Angiostatins / Q000737:chemistry; D000818:Animals; D016367:Baculoviridae / Q000235:genetics; D015374:Biosensing Techniques; D015153:Blotting, Western; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007313:Insecta; D007700:Kinetics; D008239:Lysine / Q000737:chemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D010957:Plasmids / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry*; D011956:Receptors, Cell Surface / Q000737:chemistry*; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins / Q000737:chemistry; D020349:Surface Plasmon Resonance; D013997:Time Factors; D014162:Transfection; D015032:Zinc / Q000737:chemistry; D000099053:Histidine-Rich Glycoprotein
chemical_list: C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011506:Proteins; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D011994:Recombinant Proteins; D000099053:Histidine-Rich Glycoprotein; D043168:Angiostatins; D010958:Plasminogen; D015032:Zinc; D008239:Lysine