Related Experiment Video

Updated: Jul 21, 2026

Detection of Protease Activity by Fluorescent Peptide Zymography
09:56

Detection of Protease Activity by Fluorescent Peptide Zymography

Published on: January 20, 2019

Thrombin-thrombomodulin activation of protein C facilitates the activation of progelatinase A

S R Pekovich1, P E Bock, R L Hoover

  • 1Department of Pathology, C-3321 Medical Center North, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

FEBS Letters
|April 12, 2001
PubMed

Insights

Matrix metalloproteinase progelatinase A (MMP-2) activation is linked to diseases. Activated protein C, generated via thrombin and thrombomodulin on THP-1 cells, directly cleaves and activates the MMP-2 intermediate.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Molecular Medicine

Background:

  • Matrix metalloproteinase progelatinase A (MMP-2) activation is crucial in diseases like cancer and atherosclerosis.
  • MMP-2 activation is a two-step process involving primary cleavage and secondary autocatalytic activation.
  • Thrombin can activate progelatinase A with endothelial cells.

Purpose of the Study:

  • To investigate the mechanism of cell-dependent MMP-2 activation using THP-1 cells.
  • To identify the specific molecules involved in thrombin-mediated MMP-2 activation.
  • To elucidate the role of activated protein C in MMP-2 activation.

Main Methods:

  • Utilized THP-1 cells and thrombin to study MMP-2 activation.
  • Investigated the role of thrombomodulin in the cell-dependent activation pathway.
  • Assessed the direct involvement of activated protein C in cleaving the MMP-2 intermediate.

Main Results:

  • Confirmed cell-dependent MMP-2 activation occurs with THP-1 cells.
  • Demonstrated that thrombin binds to cell-surface thrombomodulin, generating activated protein C.
  • Showed that activated protein C directly cleaves and activates the MMP-2 intermediate.

Conclusions:

  • Activated protein C is the direct activator of the MMP-2 intermediate in this pathway.
  • Established a novel link between matrix metalloproteinase activation and anti-coagulation.
  • Provided new mechanistic insights into MMP-2 activation on cell surfaces.

More Related Videos

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader07:13

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader

Published on: May 24, 2024

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation04:37

Comprehensive Analysis of Procoagulant Platelets Exhibiting Features of Necrosis, Apoptosis and Platelet Activation

Published on: May 23, 2025

Related Concept Videos

Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult body.
A...
Anticoagulant Drugs: Low-Molecular-Weight Heparins01:30

Anticoagulant Drugs: Low-Molecular-Weight Heparins

Hemostasis is a crucial process that prevents excessive blood loss from damaged blood vessels. It involves various mechanisms such as vasoconstriction, platelet adhesion and activation, and fibrin formation. The importance of each mechanism depends on the type of vessel injury. In contrast, thrombosis is the abnormal formation of a blood clot within the blood vessels, leading to potential complications if the clot obstructs blood flow. Thrombosis can be caused by increased coagulability of the...
Formation of the Platelet Plug01:22

Formation of the Platelet Plug

The platelet phase, the second stage of hemostasis, commences around 15-20 seconds after an injury. It follows and overlaps with the vascular phase, during which blood vessels constrict to minimize blood loss.
As the injured blood vessel contracts, endothelial cells undergo contraction, revealing collagen fibers in the basement membrane and underlying connective tissue. Furthermore, the plasma membrane of endothelial cells becomes adhesive, preparing the site for platelet adhesion. Platelets...
Coagulation01:09

Coagulation

The coagulation phase is a critical part of the body's process to prevent blood loss following injury to blood vessels. It involves chemical reactions that form a clot to seal the injured area. The clotting process begins shortly after injury, within 15-20 seconds for severe damage and 1-2 minutes for minor injuries.
During the coagulation phase, clotting factors, or procoagulants, play a vital role in initiating and progressing the coagulation cascade. This cascade is a series of reactions...
Extrinsic and Intrinsic Pathways of Hemostasis01:20

Extrinsic and Intrinsic Pathways of Hemostasis

Blood clotting or coagulation involves extrinsic and intrinsic pathways, which ultimately merge into the common pathway, forming a fibrin clot.
The Extrinsic Pathway
The extrinsic pathway of coagulation is typically initiated by tissue damage that exposes blood to tissue factor (TF), a protein released by the damaged tissue cells outside the blood vessels—this interaction with TF triggers biochemical reactions involving specific clotting factors. The key player here is Factor VII, which forms a...
Clot Retraction and Fibrinolysis01:16

Clot Retraction and Fibrinolysis

After a fibrin clot is formed, the next step is clot retraction, a vital process facilitated by platelet contractile proteins, such as actin and myosin. These proteins pull the fibrin strands closer together and condense the clot. This action reduces the size of the clot, creating a smaller, denser structure that effectively seals off the damaged vessel. Clot retraction consolidates the clot and helps with wound healing by bringing the edges of the damaged blood vessel closer together.