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 Experiment Videos

Multiple metalloproteinases process protransforming growth factor-alpha (proTGF-alpha).

C Leann Hinkle1, Mohita J Mohan, Peiyuan Lin

  • 1Department of Biochemistry and Biophysics, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.

Biochemistry
|February 20, 2003
PubMed
Summary
This summary is machine-generated.

Related Concept Videos

You might also read

Related Articles

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

Sort by
Same author

A Novel Small Molecule Allosteric Inhibitor of IL-17A from a DNA-Encoded Library.

ACS medicinal chemistry letters·2025
Same author

Leveraging the ADAM10 prodomain for selective inhibition to enhance recovery after myocardial infarction.

British journal of pharmacology·2025
Same author

Inner filter effect regulated upconversion sensing platform for non-invasive detection of two gastric cancer relevant substances.

Biosensors & bioelectronics·2025
Same author

SAR-444245, an engineered not-alpha IL-2 leveraging synthetic biology, modulates critical components of the immune system for durable anti-tumoral activity.

Journal of immunology (Baltimore, Md. : 1950)·2025
Same author

The IL-2 SYNTHORIN molecule promotes functionally adapted Tregs in a preclinical model of type 1 diabetes.

JCI insight·2024
Same author

A Precision Engineered Interleukin-2 for Bolstering CD8+ T- and NK-cell Activity without Eosinophilia and Vascular Leak Syndrome in Nonhuman Primates.

Cancer research communications·2024
Same journal

Aromatic Cage-Directed Azide-Methyllysine Photochemistry for Profiling Nonhistone Interacting Partners of the MeCP2 Methyl-CpG-Binding Domain.

Biochemistry·2026
Same journal

Differential Hydroxypyruvate Processing by <i>E. coli</i> and <i>P. aeruginosa</i> DXP Synthases Reveals Preferential Xylulose 5-Phosphate Formation by the <i>P. aeruginosa</i> Enzyme.

Biochemistry·2026
Same journal

Structural and Functional Characterization of Heterologous Nitrogenase Complexes.

Biochemistry·2026
Same journal

Discovery of Bacterial Unspecific Peroxygenases.

Biochemistry·2026
Same journal

Lactate Biology: Subcellular Routing and Chemical Form Define Function.

Biochemistry·2026
Same journal

Nature's Anaerobic Toolkit: Glycyl Radical Enzymes and Their Expanding Functional and Mechanistic Diversity.

Biochemistry·2026
See all related articles

Tumor necrosis factor-alpha converting enzyme (TACE) processes both TNF-alpha and N-terminal pro-transforming growth factor-alpha (TGF-alpha). However, a distinct enzyme activity, not TACE, cleaves the C-terminal site of pro-TGF-alpha.

Area of Science:

  • Molecular Biology
  • Enzymology
  • Cell Signaling

Background:

  • Tumor necrosis factor-alpha (TNF-alpha) shedding involves a single cleavage.
  • Transforming growth factor-alpha (TGF-alpha) ectodomain shedding requires N-terminal and C-terminal cleavage.
  • Tumor necrosis factor-alpha converting enzyme (TACE) is implicated in shedding both factors.

Purpose of the Study:

  • To investigate the differential processing of pro-TGF-alpha at its C-terminal site compared to TNF-alpha and N-terminal pro-TGF-alpha.
  • To identify the enzyme(s) responsible for pro-TGF-alpha C-terminal cleavage.

Main Methods:

  • Comparative analysis of hydroxamate sensitivity for TNF-alpha and pro-TGF-alpha processing.
  • Recombinant TACE activity assay on synthetic peptides representing TNF-alpha and pro-TGF-alpha cleavage sites.

Related Experiment Videos

  • Fractionation of rat liver epithelial cell membranes and characterization of enzymatic activities.
  • Analysis of ADAM 10 activity on pro-TGF-alpha peptides and soluble precursor.

    • Main Results:

    • Pro-TGF-alpha C-terminal site cleavage is less sensitive to hydroxamates than TNF-alpha processing.
    • Recombinant TACE exhibits significantly higher efficiency in cleaving TNF-alpha and N-terminal pro-TGF-alpha peptides compared to the C-terminal pro-TGF-alpha peptide.
    • Rat liver cell membranes contain two populations: one with TACE processing both sites, and another lacking TACE but cleaving the C-terminal pro-TGF-alpha site.
    • ADAM 10 efficiently cleaves N-terminal pro-TGF-alpha but not the C-terminal site.

    Conclusions:

    • TACE is an efficient N-terminal convertase for pro-TGF-alpha.
    • A distinct enzymatic activity, separate from TACE and ADAM 10, is responsible for pro-TGF-alpha C-terminal site processing.
    • This finding necessitates a revised model for TGF-alpha shedding, incorporating TACE and an unidentified C-terminal processing enzyme.