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Plasmin signaling Plasmin is a major fibrinolytic protease with wide substratespecificity. Plasminogen, a circulating plasma zymogen, can be converted toPlasmin by tissue-type Plasminogen activator ( PLAT ), Plasminogenactivator urokinase ( PLAU ), Coagulation factor XII, or Kallikrein Bplasma ( Plasma kallikrein ) [1]. Plasmin directly degrades Fibrinogen, Laminin,and Fibronectin. On the cell surface Plasmin activates a number ofMetalloproteinases ( MMPs ) [2] that degrade extracellular matrixproteins and components of basal membrane, such as Collagen, andFibrinogen, which leads to thrombolysis. Plasmin can activate or release from extracellular matrix anumber of growth factors: Vascular endothelial growth factor ( VEGF ),Transforming growth beta ( TGF-beta ), or Fibroblast growth factor ( FGF2 )[3]. These growth factors bind to their receptors on the cell surface andactivate intracellular signaling pathways that regulate cellular behavior. VEGFdirectly activates Phosphatidylinositol-3-kinase ( PI3K ) and V-akt murine thymomaviral oncogene homolog 1 ( AKT(PKB) ) signaling pathways. TGF-betaactivates Mitogen activated protein kinase p38 signaling pathway via adaptorprotein X-linked inhibitor of apoptosis ( XIAP ), Mitogen-activated protein kinasekinase kinase 7 interacting protein 1 ( TAB1 ) and Mitogen-activated proteinkinase kinase kinase 7 ( TAK1 ) kinase. Plasmin is also able to cleave TGF-beta receptor type IIIextracellular domain, suggesting possibility of yet another type of regulation of thereceptor [4]. Plasmin is inhibited by Serpin peptidase inhibitor clade I member 1 (Neuroserpin ), Serpin peptidase inhibitor clade G (C1 inhibitor) member 1 ( C1inhibitor ), T issue factor pathway inhibitor 2 ( TFPI-2 ), Pregnancy zoneprotein ( PZP ), and Serine protease inhibitor serine peptidase inhibitor Kazaltype 5 ( LEKTI ).




