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) .
Plasmin directly degrades
Laminin, and Fibronectin. On
the cell surface Plasmin activates a number of
Metalloproteinases (MMPs)  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) . 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
Plasmin is also able to cleave
TGF-beta receptor type III extracellular domain, suggesting
possibility of yet another type of regulation of the receptor .
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).
- 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
- 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
- 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
- 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