Pathway Map Details

Cell adhesion_Plasmin signaling



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Object list (links open in MetaCore):

TGF-beta receptor type I, p38 MAPK, TFPI-2, PZP, PLAT (TPA), TGF-beta receptor type II, Fibrinogen, Neuroserpin, Fibronectin, PI3K reg class IA, FGFR1, Laminin 1, Collagen IV, VEGF-A, TAB1, TGF-beta 2, LEKTI, TGF-beta receptor type III (betaglycan), PI3K cat class IA, C1 inhibitor, MEK3(MAP2K3), TGF-beta 1, Coagulation factor XII, XIAP, FGF2, TAK1(MAP3K7), Plasma kallikrein, VEGFR-2, FRS2, 3.4.21.73, Plasminogen, MMP-13, PLAU (UPA), Plasmin, MEK6(MAP2K6)

Description:

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 ), T issue 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 [electronic resource]. 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