Plasmin cleavage of vitronectin. Identification of the site and consequent attenuation in binding plasminogen activator inhibitor-1.
Plasmin is shown to specifically cleave vitronectin at the Arg361-Ser362 bond, 18 amino acid residues upstream from the site of the endogenous cleavage which gives rise to the two-chain form of vitronectin in plasma. The cleavage site is established using the exclusive phosphorylation of Ser378 with protein kinase A. As a result of the plasmin cleavage, the affinity between vitronectin and the type-1 inhibitor of plasminogen activator (PAI-1) is significantly reduced. This cleavage is stimulated by glycosaminoglycans, which are known to anchor vitronectin to the extracellular matrix. A mechanism is proposed through which plasmin can arrest its own production by feedback signalling, unleashing PAI-1 from the immobilized vitronectin found in the vascular subendothelium, which becomes exposed at the locus of a hemostatic event.
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Department of Chemical Immunology, Weizmann Institute of Science, Rehovot, Israel.
Kreizman
T
T
Shapira
H
H
Shaltiel
S
S
D000595:Amino Acid Sequence; D005109:Extracellular Matrix / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D005342:Fibrinolysis; D006023:Glycoproteins / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006493:Heparin / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008969:Molecular Sequence Data; D015849:Plasminogen Inactivators / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism; D019096:Vitronectin
D006023:Glycoproteins; D006025:Glycosaminoglycans; D015849:Plasminogen Inactivators; D019096:Vitronectin; D006493:Heparin; D011494:Protein Kinases; D005341:Fibrinolysin