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WHAT ARE PROTEASES?

Proteases, also known as proteolytic enzymes or proteinases, are enzymes essential for the regulation of numerous cellular processes, including protein degradation, immune response, and cell signaling. By breaking down proteins into smaller peptides, proteases help maintain cellular balance and respond to physiological changes.

For researchers investigating protease pathways, AnyGenes qPCR array products provide advanced tools for profiling gene expression associated with proteases and their regulatory mechanisms. These arrays offer insights into biomarkers and signaling pathways, aiding studies in disease progression and therapeutic response. By leveraging these arrays, scientists can gain a comprehensive understanding of protease activity in cellular contexts, contributing to breakthroughs in diagnostic and therapeutic solutions.

Proteases function and pathways research with AnyGenes qPCR array.

Discover our advanced qPCR arrays for Proteases research.

Protease-activated receptors (PARs) signaling. Scheme of the principal PARs-dependent signaling pathways.

Protease-activated receptors (PARs) signaling. Scheme of the principal PARs-dependent signaling pathways.

TYPES OF PROTEOLYTIC ENZYMES

Proteases can be categorized based on their active site and mechanism of action:

  • Serine Proteases: Utilize a serine residue in their active site (e.g., Trypsin)., they are involved in blood clotting and immune responses.
  • Cysteine Proteases: Use a cysteine residue (e.g., Papain).
  • Aspartic Proteases: Employ aspartate residues (e.g., Pepsin).
  • Metalloproteases: Require metal ions for activity (e.g., Carboxypeptidase), and play a vital role in tissue remodeling and inflammatory processes.

Each type plays distinct roles in biological processes and has specific applications in industries such as food processing, pharmaceuticals, and biotechnology.

MECHANISMS AND REGULATION OF PROTEASES ACTIVITY

Proteases are tightly regulated to prevent excessive or insufficient proteolysis. They function by cleaving peptide bonds between amino acids in proteins, a process that can be influenced by several factors such as Active Site Composition, Zymogen Activation (many proteases are synthesized as inactive precursors known as zymogens) and Substrate Specificity.

The regulation of protease activity is multifaceted and involves several mechanisms such as Environmental Factors (pH, Ionic Strength), Inhibitors, Complex Formation with other proteins or proteoglycans which can modulate their activity, Feedback Mechanisms (exp; in blood coagulation, the activation of one protease often leads to the activation of others in a cascade effect. This amplifies the initial signal and allows for rapid responses to physiological changes.) and Post-Translational Modifications.

PROTEASES AND SIGNALING PATHWAYS

Proteases are not only essential for protein degradation but also play critical roles as signaling molecules in various biological processes. They influence numerous signaling pathways through their ability to cleave specific substrates, including receptors and other proteins involved in cellular communication. Among this:

  • Protease-Activated Receptors (PARs), enzymes such as thrombin and trypsin activate PARs, a family of G protein-coupled receptors (GPCRs), through proteolytic cleavage.
  • Regulated Proteolysis, Certain signaling pathways, such as the Notch and Wnt pathways, depend on regulated proteolysis for their activation.
  • Cascades and Amplification, Proteases often function within cascades that amplify signals. For instance, the blood coagulation cascade involves multiple proteases that sequentially activate one another, leading to a rapid response to vascular injury..
  • Cleavage of Signaling Molecules, For example, metalloproteinases can cleave chemokines or growth factors, converting them from inactive precursors to active forms that engage their respective receptors.

IMPLICATION IN HEALTH AND DISEASES

The dysregulation of protease activity is implicated in various diseases:

  • Cancer: Proteases facilitate tumor progression by enabling cancer cell invasion and metastasis through the degradation of extracellular matrix components. They also modulate growth factor availability, influencing tumor microenvironments.
  • Inflammatory Diseases: In conditions like rheumatoid arthritis or chronic obstructive pulmonary disease (COPD), proteases contribute to tissue remodeling and inflammation by cleaving structural proteins and activating inflammatory pathways.
  • Neurodegenerative Disorders: Proteases such as β-secretase are involved in the processing of amyloid precursor protein (APP), leading to amyloid-beta accumulation, a hallmark of Alzheimer's disease. Understanding these pathways is crucial for developing targeted therapies.
(1) Zamyatnin Jr AA, Parodi A. New Advances in the Understanding of Proteases as Diagnostic and Pharmaceutical Targets in Homeostatic and Pathologic Conditions. Pharmaceutics. (2022)21;14(7):1516.
(2) Vlahos AE, et al. Protease-controlled secretion and display of intercellular signals. Nat Commun. (2022)17;13(1):912.
(3) Soleimany AP, et al. Protease Activity Analysis: A Toolkit for Analyzing Enzyme Activity Data. ACS Omega. (2022)6;7(28):24292–24301.
(4) Price R, et al. Emerging Roles of Protease-Activated Receptors (PARs) in the Modulation of Synaptic Transmission and Plasticity. Int J Mol Sci. (2021)16;22(2):869.
(5) Lalmanach G, et al. Regulation of the Proteolytic Activity of Cysteine Cathepsins by Oxidants. Int J Mol Sci. 2020 Mar 12;21(6):1944.
(6) Slack MA, Gordon SM. Protease Activity in Vascular Disease. Arterioscler Thromb Vasc Biol. (2019);39(10):e210-e218.
(7) Ong ILH, Yang KL. Recent developments in protease activity assays and sensors. Analyst. 2017 May 30;142(11):1867-1881.
(8) Vergnolle N. Protease-controlled secretion and display of intercellular signals. Gut. (2016);65(7):1215-24.
(9) Zhao P, et al. Biased signaling of protease-activated receptors. Front Endocrinol (Lausanne). (2014)13:5:67.

PROTEASES BIOMARKER LIST

Customize your own signaling pathways (SignArrays®) with the factors of your choice!
Simply download and complete our Personalized SignArrays® information file and send it at [email protected] to get started on your project.

You can check the biomarker list included in this pathway, see below:

Species : Homo sapiens (human)

Human signaling pathways

Signaling PathwaysProduct refInformations

Proteases

PRO1H1

List infos


Species : Mus musculus (mouse)

Mouse signaling pathways

Signaling PathwaysProduct refInformations

Proteases

PRO1M1

List infos


Species : Rattus norvegicus (rat)

Rat signaling pathways

Signaling PathwaysProduct refInformations

Proteases

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List In progress...


Species : Sus Scrofa (Pig)

Pig Proteases

Signaling PathwaysProduct refInformations

Proteases

*******

List In progress...


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