title: Fibrinolytic activation promoted by the cyclopentapeptide malformin: involvement of cytoskeletal reorganization.
abstract: Malformin A₁, a cyclopentapeptide of fungal origin, enhances cellular fibrinolytic activity depending on the existence of a cofactor in blood plasma. However, the nature of this cofactor remains unknown. Here, we report that vitronectin acts as a plasma cofactor of malformin A₁. We purified the cofactor from bovine plasma by activity-based fractionation, and confirmed that vitronectin in conjunction with plasminogen supports the activity of malformin A₁ to promote the fibrinolytic activity of U937 cells. Malformin A₁ action was abolished by Arg-Gly-Asp peptide (a competitor of vitronectin-integrin binding), wortmannin (an inhibitor of signaling kinases), and cytochalasin B (an inhibitor of actin polymerization). Changes in actin organization and a decrease in filopodia were observed in cells treated with malformin A₁ and plasma. A focal localization of plasminogen on the cell surface was augmented by malformin A₁, whereas the amount of cell-surface-bound plasminogen was minimally altered by the treatment. Our results suggest the involvement of cytoskeletal reorganization via vitronectin signaling in the cellular fibrinolytic activity-enhancing action of malformin A₁.
authors: Department of Applied Biological Science, Tokyo Noko University, Tokyo, Japan. ykoizumi@med.akita-u.ac.jp
authors: Yukio
authors: Y
authors: Koizumi
authors: Hirofumi
authors: H
authors: Fukudome
authors: Keiji
authors: K
authors: Hasumi
mesh_terms: D000818:Animals; D002417:Cattle; D003599:Cytoskeleton / Q000378:metabolism*; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008856:Microscopy, Fluorescence; D010456:Peptides, Cyclic / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D010456:Peptides, Cyclic; C001675:malformins