title: The plasminogen activation system in bovine milk: differential localization of tissue-type plasminogen activator and urokinase in milk fractions is caused by binding to casein and urokinase receptor.
abstract: We have analyzed the occurrence of components of the plasminogen activation system in bovine milk. Zymographic analyses showed that tissue-type plasminogen activator (t-PA) occurred in association with casein micelles, partially as a complex with type-1 plasminogen activator inhibitor (PAI-1), whereas urokinase-type plasminogen activator (u-PA) was confined to milk leukocytes. Whey contained a component with a plasminogen dependent proteolytic activity which was shown to be plasma prekallikrein (PPK). The u-PA in the milk leukocytes was shown to be bound to urokinase receptor (u-PAR). A purification to near-homogeneity of the bovine u-PAR was undertaken. Investigating the novel t-PA binding to casein micelles by ligand blotting and Sepharose immobilized casein, multimeric forms of kappa-casein and dimeric alpha s2-casein were identified as t-PA binding components. The kappa-casein gene and the fibrinogen gene are believed to have evolved from a common ancestor. Thus, the recent finding that casein enhances t-PA catalyzed plasminogen activation (Marcus, G., Hitt, S., Harvey, S.R. and Tritsch, G.L. (1993) Fibrinolysis 7, 229-236), and the observed t-PA/casein binding suggests that the casein micelle, which also contains plasminogen, may serve as a matrix for t-PA-catalyzed plasminogen activation in milk.
authors.affiliation: Department of Molecular Biology, University of Arhus, Denmark.
authors.forename: C W
authors.initials: CW
authors.lastname: Heegaard
authors.forename: L K
authors.initials: LK
authors.lastname: Rasmussen
authors.forename: P A
authors.initials: PA
authors.lastname: Andreasen
mesh_terms: D000818:Animals; D002364:Caseins / Q000378:metabolism*; D002417:Cattle; D005591:Chemical Fractionation; D008823:Micelles; D008892:Milk / Q000378:metabolism*; D010958:Plasminogen / Q000378:metabolism*; D011233:Precipitin Tests; D011288:Prekallikrein / Q000032:analysis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D010959:Tissue Plasminogen Activator / Q000032:analysis*; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis*
chemical_list: D002364:Caseins; D008823:Micelles; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010958:Plasminogen; D011288:Prekallikrein; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator