Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

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...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Coagulation protease-activated receptor-2 (PAR2) promotes dyslipidemia, obesity and MASLD through repression of the hepatic pioneer factor HNF4α.

JHEP reports : innovation in hepatology·2026
Same author

Mitral Annular Disjunction: An Under-Recognized Entity in Pediatrics.

JACC. Case reports·2024
Same author

Suppression of Heart Failure With PAR1 Pepducin Technology in a Pressure Overload Model in Mice.

Circulation. Heart failure·2023
Same author

Reply.

Hepatology (Baltimore, Md.)·2023
Same author

PAR2 promotes impaired glucose uptake and insulin resistance in NAFLD through GLUT2 and Akt interference.

Hepatology (Baltimore, Md.)·2022
Same author

Calpain-1 inhibition attenuates in vivo thrombosis in a humanized model of sickle cell disease.

Thrombosis research·2022

Related Experiment Video

Updated: May 17, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
07:13

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

Published on: May 24, 2024

Matrix metalloproteases and PAR1 activation.

Karyn M Austin1, Lidija Covic, Athan Kuliopulos

  • 1Laboratory of Hemostasis and Thrombosis, Molecular Oncology Research Institute, Tufts University School of Medicine, Tufts Medica lCenter, Boston, MA 02111, USA.

Blood
|October 23, 2012
PubMed
Summary

Matrix metalloproteases (MMPs) activate Protease-activated receptor-1 (PAR1) through novel mechanisms, impacting cardiovascular diseases. Inhibiting MMP-PAR1 signaling offers therapeutic potential for vascular conditions.

More Related Videos

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography
07:32

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography

Published on: March 30, 2022

Related Experiment Videos

Last Updated: May 17, 2026

Characterizing Modulators of Protease-Activated Receptors with a Calcium Mobilization Assay Using a Plate Reader
07:13

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

Published on: May 24, 2024

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity
07:09

Myeloid Innate Signaling Pathway Regulation by MALT1 Paracaspase Activity

Published on: January 7, 2019

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography
07:32

Bacterial Expression and Purification of Human Matrix Metalloproteinase-3 using Affinity Chromatography

Published on: March 30, 2022

Area of Science:

  • Biochemistry
  • Cardiovascular Biology
  • Molecular Pharmacology

Background:

  • Cardiovascular diseases, including atherothrombosis, are a major global health burden.
  • Matrix metalloproteases (MMPs) play emerging roles in platelet and endothelial function relevant to atherothrombosis.
  • Protease-activated receptor-1 (PAR1) is a key G protein-coupled receptor in vascular biology.

Purpose of the Study:

  • To elucidate the noncanonical activation of PAR1 by MMPs.
  • To contrast canonical thrombin-mediated PAR1 activation with MMP-induced activation.
  • To explore the role of MMP-PAR1 signaling in vascular diseases and its therapeutic implications.

Main Methods:

  • Investigated the cleavage sites of PAR1 by MMP-1 and MMP-13.
  • Analyzed the distinct signaling pathways activated by canonical and noncanonical PAR1 agonists.
  • Examined the contribution of MMP-PAR1 signaling to various vascular pathologies.

Main Results:

  • MMP-1 and MMP-13 cleave PAR1 at noncanonical sites, generating unique tethered ligands.
  • This noncanonical activation leads to metalloprotease-specific signaling patterns, termed biased agonism.
  • Distinct functional outputs are observed depending on the activating protease.

Conclusions:

  • MMP-mediated PAR1 activation represents a novel signaling paradigm in vascular biology.
  • Targeting MMP-PAR1 interactions holds therapeutic promise for atherothrombotic disease, in-stent restenosis, heart failure, and sepsis.
  • Understanding biased agonism in PAR1 signaling is crucial for developing targeted therapies.