Cell adhesion - Plasmin signaling

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Plasmin signaling

Plasmin is a major fibrinolytic protease with wide substrate specificity.

Plasminogen, a circulating plasma zymogen, can be converted to Plasmin by tissue-type Plasminogen activator (PLAT), Plasminogen activator urokinase (PLAU), Coagulation factor XII, or Kallikrein B plasma (Plasma kallikrein) [1].

Plasmin directly degrades Fibrinogen, Laminin, and Fibronectin. On the cell surface Plasmin activates a number of Metalloproteinases (MMPs) [2] that degrade extracellular matrix proteins and components of basal membrane, such as Collagen, and Fibrinogen, which leads to thrombolysis.

Plasmin can activate or release from extracellular matrix a number 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 and activate intracellular signaling pathways that regulate cellular behavior. VEGF directly activates Phosphatidylinositol-3-kinase (PI3K) and V-akt murine thymoma viral oncogene homolog 1 (AKT(PKB)) signaling pathways. TGF-beta activates Mitogen activated protein kinase p38 signaling pathway via adaptor protein X-linked inhibitor of apoptosis (XIAP), Mitogen-activated protein kinase kinase kinase 7 interacting protein 1 (TAB1) and Mitogen-activated protein kinase kinase kinase 7 (TAK1) kinase.

Plasmin is also able to cleave TGF-beta receptor type III extracellular domain, suggesting possibility of yet another type of regulation of the receptor [4].

Plasmin is inhibited by Serpin peptidase inhibitor clade I member 1 (Neuroserpin), Serpin peptidase inhibitor clade G (C1 inhibitor) member 1 (C1 inhibitor), Tissue factor pathway inhibitor 2 (TFPI-2), Pregnancy zone protein (PZP), and Serine protease inhibitor serine peptidase inhibitor Kazal type 5 (LEKTI).

References:

  1. Kranenburg O, Bouma B, Kroon-Batenburg LM, Reijerkerk A, Wu YP, Voest EE, Gebbink MF
    Tissue-type plasminogen activator is a multiligand cross-beta structure receptor. Current biology : CB 2002 Oct 29;12(21):1833-9
  2. Morgan H, Hill PA
    Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity. Cancer cell international 2005 Feb 8;5(1):1
  3. Ribatti D, Leali D, Vacca A, Giuliani R, Gualandris A, Roncali L, Nolli ML, Presta M
    In vivo angiogenic activity of urokinase: role of endogenous fibroblast growth factor-2. Journal of cell science 1999 Dec;112 ( Pt 23):4213-21
  4. Lamarre J, Vasudevan J, Gonias SL
    Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-beta complex from the cell surface. The Biochemical journal 1994 Aug 15;302 ( Pt 1):199-205

  1. Kranenburg O, Bouma B, Kroon-Batenburg LM, Reijerkerk A, Wu YP, Voest EE, Gebbink MF
    Tissue-type plasminogen activator is a multiligand cross-beta structure receptor. Current biology : CB 2002 Oct 29;12(21):1833-9
  2. Morgan H, Hill PA
    Human breast cancer cell-mediated bone collagen degradation requires plasminogen activation and matrix metalloproteinase activity. Cancer cell international 2005 Feb 8;5(1):1
  3. Ribatti D, Leali D, Vacca A, Giuliani R, Gualandris A, Roncali L, Nolli ML, Presta M
    In vivo angiogenic activity of urokinase: role of endogenous fibroblast growth factor-2. Journal of cell science 1999 Dec;112 ( Pt 23):4213-21
  4. Lamarre J, Vasudevan J, Gonias SL
    Plasmin cleaves betaglycan and releases a 60 kDa transforming growth factor-beta complex from the cell surface. The Biochemical journal 1994 Aug 15;302 ( Pt 1):199-205

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