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Lipoprotein(a) Binds to Fibronectin and Has Serine Proteinase Activity Capable of Cleaving It

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Journal EMBO J
Date 1989 Dec 20
PMID 2531657
Citations 11
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Abstract

The plasma concentration of human lipoprotein(a) [Lp(a)] is correlated with the risk of heart disease. A distinct feature of the Lp(a) particle is the apolipoprotein (a) [apo(a)], which is associated with apoB-100, the main protein component of low-density lipoprotein. We now report that apo(a), which has extensive homology to plasminogen, binds to immobilized fibronectin. The binding of Lp(a) was localized to the C-terminal heparin-binding domain of fibronectin. Incubation of Lp(a) with fibronectin resulted in fragmentation of fibronectin. The cleavage pattern, as visualized by gel electrophoresis and immunoblotting, was reproducibly obtained with Lp(a) purified from five different individuals and was distinct from that obtained upon proteolysis of fibronectin by plasmin or kallikrein. The use of synthetic peptide substrates demonstrated that the amino acid specificity for Lp(a) was arginine rather than lysine. The proteolytic activity of Lp(a) was localized to apo(a) and experiments with inhibitors indicated that the proteolytic activity was of serine proteinase-type.

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References
1.
Vaheri A, Salonen E, Vartio T . Fibronectin in formation and degradation of the pericellular matrix. Ciba Found Symp. 1985; 114:111-26. DOI: 10.1002/9780470720950.ch8. View

2.
PANDE H, Calaycay J, Lee T, Legesse K, Shively J, Siri A . Demonstration of structural differences between the two subunits of human-plasma fibronectin in the carboxy-terminal heparin-binding domain. Eur J Biochem. 1987; 162(2):403-11. DOI: 10.1111/j.1432-1033.1987.tb10616.x. View

3.
Smith P, Krohn R, Hermanson G, Mallia A, Gartner F, Provenzano M . Measurement of protein using bicinchoninic acid. Anal Biochem. 1985; 150(1):76-85. DOI: 10.1016/0003-2697(85)90442-7. View

4.
Borsi L, Castellani P, Balza E, Siri A, Pellecchia C, De Scalzi F . Large-scale procedure for the purification of fibronectin domains. Anal Biochem. 1986; 155(2):335-45. DOI: 10.1016/0003-2697(86)90443-4. View

5.
Rhoads G, Dahlen G, Berg K, Morton N, Dannenberg A . Lp(a) lipoprotein as a risk factor for myocardial infarction. JAMA. 1986; 256(18):2540-4. View