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.
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.
Heegaard
C W
CW
Department of Molecular Biology, University of Arhus, Denmark.
Rasmussen
L K
LK
Andreasen
P A
PA
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*
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