Plasmin cleavage of vitronectin Identification of the site and consequent attenuation in binding plasminogen activator inhibitor‐1

FEBS Letters

Kreizman, Tamar¹  Chain, Daniel¹  Shaltiel, Shmuel¹  Shapira, Hadar¹ 

[1] Department of Chemical Immunology, The Weizmann Institute of Science, Rehovot, 76100, Israel

关键词: Fibrinolysis;    PAI-1;    Protein kinase-A;    Heparin;    Extracellular matrix;    PAI-1;    plasminogen activator inhibitor-1;    PKA;    cAMP dependent protein kinase (catalytic subunit);    V;    vitronectin (M r in kDa indicated by subscript);    Vn;    pure vitronectin as isolated from plasma (containing V75 and V65 + 10);    Vn′;    plasmin-clipped Vn;   

DOI  :  10.1016/0014-5793(91)80810-P

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown