Activation of extracellular transglutaminase 2 by thioredoxin.

ABSTRACT: The mechanism of activation of transglutaminase 2 (TG2) in the extracellular matrix remains a fundamental mystery in our understanding of the biology of this multifunctional mammalian enzyme. Earlier investigations have highlighted the role of a disulfide bond formed by vicinal Cys residues in maintaining calcium-bound TG2 in an inactive state. Here, we have shown that the redox potential of this disulfide bond is approximately -190 mV, a high value for a disulfide bond in proteins. Consistent with this observation, TG2 activity in a freshly wounded fibroblast culture depends upon the redox potential of the environment. We sought to identify a physiological mechanism for the activation of oxidized TG2. With a k(cat)/K(m) of 1.6 μm(-1) min(-1), human thioredoxin (Trx) was a highly specific

SUBMITTER: Jin X 

PROVIDER: S-EPMC3199528 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature