Structure and function of plasminogen/plasmin system

The main physiological function of plasmin is blood clot fibrinolysis and restoration of normal blood flow. To date, however, it became apparent that in addition to thrombolysis, the plasminogen/plasmin system plays an important physiological and pathological role in a number of other essential processes: degradation of the extracellular matrix, embryogenesis, cell migration, tissue remodeling, wound healing, angiogenesis, inflammation, and tumor cell migration. This review focuses on structural features of plasminogen, regulation of its activation by physiological plasminogen activators, inhibitors of plasmin, and plasminogen activators, and the role of plasminogen binding to fibrin, cellular receptors, and extracellular ligands in various functions performed by plasmin thus formed.

[1]  E. Pryzdial,et al.  Plasmin Converts Factor X from Coagulation Zymogen to Fibrinolysis Cofactor* , 1999, The Journal of Biological Chemistry.

[2]  L. Miles,et al.  Plasminogen Receptors: The First Quarter Century , 2013, Seminars in Thrombosis & Hemostasis.

[3]  S. Serratì,et al.  The plasminogen activation system in inflammation. , 2008, Frontiers in bioscience : a journal and virtual library.

[4]  K. Hartshorn,et al.  Tetranectin Binds to the Kringle 1-4 Form of Angiostatin and Modifies Its Functional Activity , 2004, Journal of biomedicine & biotechnology.

[5]  L. Lund,et al.  Plasminogen activation and cancer , 2005, Thrombosis and Haemostasis.

[6]  P. Carmeliet,et al.  Urokinase-type plasminogen activator is effective in fibrin clearance in the absence of its receptor or tissue-type plasminogen activator. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Waisman.  Plasminogen: Structure, Activation, and Regulation , 2003, Springer US.

[8]  H. Pannekoek,et al.  Structure of plasminogen activator inhibitor 1 (PAI-1) and its function in fibrinolysis: an update , 1995 .

[9]  Yihai Cao,et al.  Therapeutic potentials of angiostatin in the treatment of cancer. , 1999, Haematologica.

[10]  J. Folkman,et al.  Angiostatin induces and sustains dormancy of human primary tumors in mice , 1996, Nature Medicine.

[11]  J. Vassalli.  The Urokinase Receptor , 1994 .

[12]  J. Morrow,et al.  Differential effects of angiotensin converting enzyme inhibitors on the vasodepressor and prostacyclin responses to bradykinin. , 1996, The Journal of pharmacology and experimental therapeutics.

[13]  T. Tuan,et al.  Plasminogen activator/plasmin system: A major player in wound healing? , 2003, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[14]  D. Saunders,et al.  Plasminogen binding and activation at the breast cancer cell surface: the integral role of urokinase activity , 2007, Breast Cancer Research.

[15]  R. Aisina,et al.  Mechanism of action of θ-amino acids on plasminogen activation and fibrinolysis induced by staphylokinase , 2007, Biochemistry (Moscow).

[16]  P. Burtin,et al.  The plasmin system in human colonic tumors: An immunofluorescence study , 1985, International journal of cancer.

[17]  S. Kimura,et al.  Cross-linking site in fibrinogen for alpha 2-plasmin inhibitor. , 1986, The Journal of biological chemistry.

[18]  F. Castellino,et al.  Critical role for conversion of glu-plasminogen to Lys-plasminogen for optimal stimulation of plasminogen activation on cell surfaces. , 2003, Trends in cardiovascular medicine.

[19]  Y. Takada,et al.  Effects of tranexamic acid on fibrinolysis, fibrinogenolysis and amidolysis. , 1986, Thrombosis research.

[20]  T. Simmet,et al.  Novel aspects and new roles for the serine protease plasmin , 2004, Cellular and Molecular Life Sciences CMLS.

[21]  H. Wu,et al.  The binding of plasminogen fragments to cultured human umbilical vein endothelial cells. , 1992, Biochemical and biophysical research communications.

[22]  M. Hoylaerts,et al.  Fibrinolytic properties of one-chain and two-chain human extrinsic (tissue-type) plasminogen activator. , 1982, The Journal of biological chemistry.

[23]  N. Booth,et al.  TAFIa, PAI‐1 and α2‐antiplasmin: complementary roles in regulating lysis of thrombi and plasma clots , 2007, Journal of thrombosis and haemostasis : JTH.

[24]  F. Castellino,et al.  Structure and function of the plasminogen/plasmin system , 2005, Thrombosis and Haemostasis.

[25]  G. Soff.  Angiostatin and Angiostatin-related Proteins , 2004, Cancer and Metastasis Reviews.

[26]  H. Lijnen,et al.  Issue Editorial Focus : Issue Editorial Focus , 2005 .

[27]  C. Clavel,et al.  Detection of the plasmin system in human mammary pathology using immunofluorescence. , 1986, Cancer research.

[28]  C. Francis.  Plasminogen activator inhibitor-1 levels and polymorphisms. , 2002, Archives of pathology & laboratory medicine.

[29]  A. Wear.  CIRCULATION , 1964, The Lancet.

[30]  D. Davidson,et al.  The influence of the nature of the asparagine 289-linked oligosaccharide on the activation by urokinase and lysine binding properties of natural and recombinant human plasminogens. , 1993, The Journal of clinical investigation.

[31]  P. Gaffney,et al.  Fibrinolysis : current fundamental and clinical concepts , 1978 .

[32]  M. Hoylaerts,et al.  Isolation and characterization of a human plasma protein with affinity for the lysine binding sites in plasminogen. Role in the regulation of fibrinolysis and identification as histidine-rich glycoprotein. , 1980, The Journal of biological chemistry.

[33]  H. Dvorak,et al.  Angiogenesis: update 2005 , 2005, Journal of thrombosis and haemostasis : JTH.

[34]  B. Binder.  Physiology and pathophysiology of the fibrinolytic system , 1995 .

[35]  V. Díaz,et al.  Specific interaction of tissue-type plasminogen activator (t-PA) with annexin II on the membrane of pancreatic cancer cells activates plasminogen and promotes invasion in vitro , 2004, Gut.

[36]  H. Wu,et al.  Interaction of plasminogen and fibrin in plasminogen activation. , 1990, The Journal of biological chemistry.

[37]  B. Wiman,et al.  On the specific interaction between the lysine-binding sites in plasmin and complementary sites in alpha2-antiplasmin and in fibrinogen. , 1979, Biochimica et biophysica acta.

[38]  H. Birkedal‐Hansen,et al.  Matrix metalloproteinases: a review. , 1993, Critical reviews in oral biology and medicine : an official publication of the American Association of Oral Biologists.

[39]  D. Collen,et al.  Proteolytic cleavage of urokinase-type plasminogen activator by stromelysin-1 (MMP-3). , 1998, Biochemistry.

[40]  K. Hajjar,et al.  Molecular mechanisms of fibrinolysis , 2005, British journal of haematology.

[41]  Jordi Félez,et al.  Role of cell-surface lysines in plasminogen binding to cells: identification of alpha-enolase as a candidate plasminogen receptor. , 1991, Biochemistry.

[42]  R. Aisina,et al.  The role of carbohydrate side chains of plasminogen in its activation by staphylokinase. , 2005, Biochimica et biophysica acta.

[43]  J. Cash.  Fibrinolysis , 1971, Il Sangue.

[44]  J. Szemraj,et al.  Angiotensin II enhances thrombosis development in renovascular hypertensive rats , 2005, Thrombosis and Haemostasis.

[45]  R. Aisina,et al.  The in vitro cross-effects of inhibitors of renin-angiotensin and fibrinolytic systems on the key enzymes of these systems , 2008, Russian Journal of Bioorganic Chemistry.

[46]  D. Loskutoff,et al.  Plasminogen Has a Broad Extrahepatic Distribution , 2002, Thrombosis and Haemostasis.

[47]  J. Melchor,et al.  Tissue plasminogen activator in central nervous system physiology and pathology , 2005, Thrombosis and Haemostasis.

[48]  J. Rak,et al.  The hemostatic system and angiogenesis in malignancy. , 2001, Neoplasia.

[49]  M. K. Young,et al.  Purification and Characterization of A61 , 2001, The Journal of Biological Chemistry.

[50]  K. Nogami,et al.  Plasmin-induced procoagulant effects in the blood coagulation: a crucial role of coagulation factors V and VIII , 2010, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[51]  M. Saraste,et al.  FEBS Lett , 2000 .

[52]  D. Rijken,et al.  Basic principles in thrombolysis: regulatory role of plasminogen. , 2001, Thrombosis research.

[53]  Michael Simons,et al.  Antiangiogenic plasma activity in patients with systemic sclerosis. , 2007, Arthritis and rheumatism.

[54]  M. Blaber,et al.  Human tissue kallikreins 3 and 5 can act as plasminogen activator releasing active plasmin. , 2013, Biochemical and Biophysical Research Communications - BBRC.

[55]  W. Nieuwenhuizen,et al.  Molecular mechanisms of initiation of fibrinolysis by fibrin , 2003, Thrombosis and Haemostasis.

[56]  M. Stack,et al.  Angiostatin inhibits endothelial and melanoma cellular invasion by blocking matrix-enhanced plasminogen activation. , 1999, The Biochemical journal.

[57]  Dr. Andreas von Deimling.  Neoplasia , 1997, Laboratory investigation; a journal of technical methods and pathology.

[58]  A. Gils,et al.  Fibrinogen Contains Cryptic PAI-1 Binding Sites That Are Exposed on Binding to Solid Surfaces or Limited Proteolysis , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[59]  D. Collen,et al.  Mechanisms of physiological fibrinolysis. , 1995, Bailliere's clinical haematology.

[60]  N. Booth.  Regulation of fibrinolytic activity by localization of inhibitors to fibrin(ogen) , 2000 .

[61]  T. L. Moser,et al.  Angiostatin binds ATP synthase on the surface of human endothelial cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[62]  P. Kovanen,et al.  Activation of interstitial collagenase, MMP‐1, by Staphylococcus aureus cells having surface‐bound plasmin: a novel role of plasminogen receptors of bacteria , 1999, FEBS letters.

[63]  M. Stack,et al.  The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin , 1997 .

[64]  Hua-Lin Wu,et al.  Anti-angiogenesis mediated by angiostatin K1–3, K1–4 and K1–4.5 , 2006, Thrombosis and Haemostasis.

[65]  I. Clemmensen,et al.  Adsorption to fibrin of native fragments of known primary structure from human plasminogen. , 1981, Biochimica et biophysica acta.

[66]  H. Ha,et al.  The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases , 2009, Nature Reviews Nephrology.

[67]  H. Wu,et al.  Suppression of angiogenesis and tumor growth by the inhibitor K1-5 generated by plasmin-mediated proteolysis. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[68]  M. Duffy.  Urokinase-type plasminogen activator and malignancy , 1993 .

[69]  W. Stetler-Stevenson,et al.  Structural biochemistry and activation of matrix metalloproteases. , 1993, Current opinion in cell biology.

[70]  J. Stuart.  Fibrinolysis: Current Fundamental and Clinical Concepts , 1979 .

[71]  G. Murphy,et al.  The role of plasminogen in cell-mediated collagen degradation. , 1989, Cell biology international reports.

[72]  J. Kuiper,et al.  Mechanisms of Tissue‐type Plasminogn Activator (tPA) Clearance by the Liver a , 1992, Annals of the New York Academy of Sciences.

[73]  J. Whisstock,et al.  New insights into the structure and function of the plasminogen/plasmin system. , 2013, Current opinion in structural biology.

[74]  M. Ploug.  Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor. , 2003, Current pharmaceutical design.

[75]  C. Ponting,et al.  Plasminogen: a structural review. , 1992, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[76]  T. Starzl,et al.  Synthesis of human plasminogen by the liver. , 1980, Science.

[77]  P. Burtin,et al.  The plasmin system in human adenocarcinomas and their metastases. A comparative immunofluorescence study , 1987, International journal of cancer.

[78]  F. Young.  Biochemistry , 1955, The Indian Medical Gazette.