Effects of histidine-proline-rich glycoprotein on plasminogen activation in solution and on surfaces.
Histidine-proline-rich glycoprotein (HPRG) has long been known to associate with plasminogen (Plg) in solution, but the consequences of this interaction have not been defined. Here we show that HPRG adsorbed to a glycosaminoglycan (GAG) surface also binds Plg with a Kd value of 0.7 micromol/l. Moreover, we present evidence that HPRG acts as a modulator of the activation of Plg by tissue-type Plg activator. Specifically, Plg complexed with HPRG on a GAG surface is more readily activated by tissue-type Plg activator than free Plg, with a 10-fold difference in apparent catalytic efficiency (kcat/Km). HPRG also augments the increase in Plg activation caused by fibrinogen fragments either in solution or on GAG surfaces. In contrast, HPRG abrogates the stimulatory effects of fibrinogen on Plg activation in solution. These observations demonstrate that HPRG can act as either a positive or negative effector of Plg activation in vitro and may serve as a modulator of fibrinolysis in vivo.
Borza
Dorin-Bogdan
DB
Division of Molecular Biology and Biochemistry, School of Biological Sciences, University of Missouri-Kansas City, Kansas City, Missouri 64110-2499, USA.
Shipulina
Natalia V
NV
Morgan
William T
WT
D000327:Adsorption; D002384:Catalysis; D006023:Glycoproteins / Q000737:chemistry* / Q000378:metabolism; D006025:Glycosaminoglycans / Q000737:chemistry; D006639:Histidine; D006801:Humans; D010446:Peptide Fragments; D010958:Plasminogen / Q000737:chemistry* / Q000378:metabolism; D011392:Proline; D011485:Protein Binding; D012996:Solutions; D013499:Surface Properties; D010959:Tissue Plasminogen Activator / Q000378:metabolism
D006023:Glycoproteins; D006025:Glycosaminoglycans; D010446:Peptide Fragments; D012996:Solutions; D006639:Histidine; D010958:Plasminogen; D011392:Proline; D010959:Tissue Plasminogen Activator