Osteonectin in matrix remodeling. A plasminogen-osteonectin-collagen complex.
Osteonectin is an adhesive glycoprotein synthesized constitutively by osteoblasts, endothelial cells, and megakaryocytes. Bone-derived and platelet-derived osteonectins differ in their electrophoretic mobility and carbohydrate content, and each displays different affinities for collagen matrices. Both types of osteonectin bind to plasminogen (Kd(app), of 4.7 +/- 1.0 x 10(-8) M for bone osteonectin and 1.2 +/- 0.1 x 10(-7) M for platelet osteonectin). The osteonectin-plasminogen interaction is inhibited by alpha 2-antiplasmin and epsilon-aminocaproic acid, suggesting that the interaction is mediated through the kringle 1 region of plasminogen. Both osteonectins enhance the rate of plasmin generation by tissue-type plasminogen activator to approximately the same extent as fibrinogen. Equilibrium binding measurements conducted using total internal reflection fluorescence spectroscopy indicate that plasminogen binds to collagen in the presence of bone osteonectin (Kd = 1.30 +/- 0.1 x 10(-7) M). No binding of plasminogen to collagen matrix was detected in the presence of platelet osteonectin or in the absence of bone osteonectin. Bone osteonectin-dependent binding of plasminogen to collagen matrix is reversed by the addition of epsilon-aminocaproic acid. The ability of both types of osteonectin to bind to and influence plasminogen activation and of bone osteonectin to anchor plasminogen on collagen matrices suggests that osteonectin may play a role in directing extracellular matrix proteolysis.
Kelm
R J
RJ
University of Vermont, Department of Biochemistry, College of Medicine, Burlington 05405.
Swords
N A
NA
Orfeo
T
T
Mann
K G
KG
D015119:Aminocaproic Acid / Q000494:pharmacology; D001667:Binding, Competitive; D001792:Blood Platelets / Q000378:metabolism*; D001842:Bone and Bones / Q000378:metabolism*; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007700:Kinetics; D015676:Osteonectin / Q000737:chemistry / Q000378:metabolism*; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D000979:alpha-2-Antiplasmin / Q000494:pharmacology
D015676:Osteonectin; D000979:alpha-2-Antiplasmin; D010958:Plasminogen; D003094:Collagen; D010959:Tissue Plasminogen Activator; D015119:Aminocaproic Acid