Extracellular transglutaminase 2 is catalytically inactive, but is transiently activated upon tissue injury

Transglutaminase 2 (TG2) is a multifunctional mammalian protein with transamidase and signaling properties. Using selective TG2 inhibitors and tagged nucleophilic amine substrates, we show that the majority of extracellular TG2 is inactive under normal physiological conditions in cell culture and in...

Full description

Saved in:
Bibliographic Details
Published in:PloS one 2008-03, Vol.3 (3), p.e1861
Main Authors: Siegel, Matthew, Strnad, Pavel, Watts, R Edward, Choi, Kihang, Jabri, Bana, Omary, M Bishr, Khosla, Chaitan
Format: Article
Language:English
Subjects:
Activation
Binding Sites
Biochemistry
Catalysis
Celiac disease
Cell culture
Cell Line
Chemical engineering
Chemistry
Disease
Enzyme Inhibitors - pharmacology
Enzymes
Fibroblasts
Gastroenterology and Hepatology
Gluten
Immune system
Injuries
Intestine
Intestine, Small - drug effects
Intestine, Small - enzymology
Liver
Liver - drug effects
Liver - enzymology
Localization
Mice
Mucosa
Oxazoles - pharmacology
Peptides
Physiological aspects
Poly (I:C)
Proteins
Small intestine
Substrates
TLR3 protein
Toll-like receptors
Transglutaminase 2
Transglutaminases - antagonists & inhibitors
Transglutaminases - metabolism
Type 2 diabetes
Wounding
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Transglutaminase 2 (TG2) is a multifunctional mammalian protein with transamidase and signaling properties. Using selective TG2 inhibitors and tagged nucleophilic amine substrates, we show that the majority of extracellular TG2 is inactive under normal physiological conditions in cell culture and in vivo. However, abundant TG2 activity was detected around the wound in a standard cultured fibroblast scratch assay. To demonstrate wounding-induced activation of TG2 in vivo, the toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly(I:C)), was injected in mice to trigger small intestinal injury. Although no TG2 activity was detected in vehicle-treated mice, acute poly(I:C) injury resulted in rapid TG2 activation in the small intestinal mucosa. Our findings provide a new basis for understanding the role of TG2 in physiology and disease.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0001861