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:
- 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
