TY - JOUR
T1 - Binding and endocytosis of plasminogen activator/ serpin complexes by very low density lipoprotein receptor
AU - Heegaard, Christian W.
AU - Kasza, Aneia
AU - Petersen, Helle H.
AU - Simonsen, Anna C.W.
AU - Oka, Kazuhiro
AU - Chan, Lawrence
AU - Andreasen, Peter A.
PY - 1996/12/1
Y1 - 1996/12/1
N2 - Very low density lipoprotein receptor (VLDLR) is a recently cloned member of a family of multifunctional endocytosis receptors, which includes the low density lipoprotein receptor (LDLR), the os-macroglobulin receptor/LDLRrelated protein (LRP), and gp330. The exact physiological function(s) of VLDLR have not been clarified yet. However, VLDLR has previously been shown to bind lipoproteins containing apoE, the receptor-associated protein (RAP), and uPA/PAI-1 complex. We have studied the specificity of binding and endocytosis by VLDLR among a variety of proteinase/inhibitor complexes, including various combinations of the serine proteinases plasmin, tPA, uPA, LMW-uPA, and plasma kallikrein with the serpins PAI-1, PA1-2, protein C inhibitor, Cl-inhibitor, and a2-antiplasmin. VLDLR from bovine mammary gland was purified by ligand affinity chromatography with RAP. Binding was measured by ligand blotting analysis. Endocytosis was estimated by measuring RAP-sensitive degradation of radiolabelled complexes by CHO cells transfected with VLDLR cDNA. We found that VLDLR binds all combinations of plasminogen activators with PAI-1 and protein C inhibitor, while complex of many serine proteinases with their primary inhibitor, i.e. plasmin/a,-antiplasmin complex, did not bind. The binding results show that both the serine proteinase and the serpin moiety contributed to the binding specificity. We conclude that the physiological function of VLDLR may include clearance of various plasminogen activator/inhibitor complexes.
AB - Very low density lipoprotein receptor (VLDLR) is a recently cloned member of a family of multifunctional endocytosis receptors, which includes the low density lipoprotein receptor (LDLR), the os-macroglobulin receptor/LDLRrelated protein (LRP), and gp330. The exact physiological function(s) of VLDLR have not been clarified yet. However, VLDLR has previously been shown to bind lipoproteins containing apoE, the receptor-associated protein (RAP), and uPA/PAI-1 complex. We have studied the specificity of binding and endocytosis by VLDLR among a variety of proteinase/inhibitor complexes, including various combinations of the serine proteinases plasmin, tPA, uPA, LMW-uPA, and plasma kallikrein with the serpins PAI-1, PA1-2, protein C inhibitor, Cl-inhibitor, and a2-antiplasmin. VLDLR from bovine mammary gland was purified by ligand affinity chromatography with RAP. Binding was measured by ligand blotting analysis. Endocytosis was estimated by measuring RAP-sensitive degradation of radiolabelled complexes by CHO cells transfected with VLDLR cDNA. We found that VLDLR binds all combinations of plasminogen activators with PAI-1 and protein C inhibitor, while complex of many serine proteinases with their primary inhibitor, i.e. plasmin/a,-antiplasmin complex, did not bind. The binding results show that both the serine proteinase and the serpin moiety contributed to the binding specificity. We conclude that the physiological function of VLDLR may include clearance of various plasminogen activator/inhibitor complexes.
UR - http://www.scopus.com/inward/record.url?scp=33846658768&partnerID=8YFLogxK
M3 - Journal article
AN - SCOPUS:33846658768
SN - 0268-9499
VL - 10
JO - Fibrinolysis
JF - Fibrinolysis
IS - SUPPL. 3
ER -