title: Leishmania mexicana: LACK (Leishmania homolog of receptors for activated C-kinase) is a plasminogen binding protein.
abstract: Leishmania mexicana is able to interact with the fibrinolytic system through its component plasminogen, the zymogenic form of the protease plasmin. In this study a new plasminogen binding protein of this parasite was identified: LACK, the Leishmania homolog of receptors for activated C-kinase. Plasminogen binds recombinant LACK with a K(d) value of 1.6±0.4 μM, and binding is lysine-dependent since it is inhibited by the lysine analog ε-aminocaproic acid. Inhibition studies with specific peptides and plasminogen binding activity of a mutated recombinant LACK have highlighted the internal motif (260)VYDLESKAV(268), similar to those found in several enolases, as involved in plasminogen binding. Recombinant LACK and secreted proteins, in medium conditioned by parasites, enhance plasminogen activation to plasmin by the tissue plasminogen activator (t-PA). In addition to its localization in the cytosol, in the microsomal fraction and as secreted protein in conditioned medium, LACK was also localized on the external surface of the membrane. The results presented here suggest that LACK might bind and enhance plasminogen activation in vivo promoting the formation of plasmin. Plasminogen binding of LACK represents a new function for this protein and might contribute to the invasiveness of the parasite.
authors.affiliation: Laboratorio de Fisiología, Facultad de Ciencias, Universidad de Los Andes, La Hechicera, Mérida 5101, Venezuela.
authors.forename: Amaranta
authors.initials: A
authors.lastname: Gómez-Arreaza
authors.forename: Héctor
authors.initials: H
authors.lastname: Acosta
authors.forename: Ximena
authors.initials: X
authors.lastname: Barros-Álvarez
authors.forename: Juan L
authors.initials: JL
authors.lastname: Concepción
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Luisana
authors.initials: L
authors.lastname: Avilan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015153:Blotting, Western; D015180:Electrophoresis, Gel, Two-Dimensional; D005455:Fluorescent Antibody Technique; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D007894:Leishmania mexicana / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D010958:Plasminogen / Q000378:metabolism*; D015800:Protozoan Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011817:Rabbits; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
chemical_list: D000953:Antigens, Protozoan; D007106:Immune Sera; D015800:Protozoan Proteins; D011994:Recombinant Proteins; C093139:LACK antigen, Leishmania; D010958:Plasminogen