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Plasmin cleavage of vitronectin Identification of the site and consequent attenuation in binding plasminogen activator inhibitor‐1
Author(s) -
Chain Daniel,
Kreizman Tamar,
Shapira Hadar,
Shaltiel Shmuel
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80810-p
Subject(s) - vitronectin , plasmin , chemistry , cleavage (geology) , attenuation , binding site , plasminogen activator , fibrinolysis , biochemistry , microbiology and biotechnology , medicine , biology , enzyme , receptor , physics , integrin , optics , paleontology , fracture (geology)
Plasmin is shown to specifically cleave vitronectin at the Arg 361 ‐Ser 362 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 Ser 378 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.