GTP is required to stabilize and display transamidation activity of transglutaminase 2

Biochem Biophys Res Commun. 2002 Jun 21;294(4):818-22. doi: 10.1016/S0006-291X(02)00582-X.

Abstract

Transglutaminase 2 (TGase 2) is a bifunctional enzyme that catalyzes calcium-dependent transamidation and GTP binding/hydrolysis. The transamidation activity is proposed to be associated with several neurodegenerative disorders such as Alzheimer's and Hungtinton's disease. However, the regulation mechanism by which TGase 2 causes neurodegeneration is unknown. In this study, we show that two activities of TGase 2 have a differential stability; transamidation activity is less stable than GTP hydrolytic activity, and that GTP was required to stabilize and to display transamidation activity. Moreover, GTP binding-defective mutant of TGase 2 did not show any transamidation activity in transfection experiments. These results indicate that GTP binding is crucial for transamidation activity of TGase 2, suggesting that protein cross-linking by TGase 2 might be associated with G-protein coupled receptor signaling system. Thus, our data could contribute to understand the regulation of TGase 2 activity and TGase 2-associated pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Animals
  • Erythrocytes / enzymology
  • GTP-Binding Proteins / isolation & purification
  • GTP-Binding Proteins / metabolism*
  • GTP-Binding Proteins / physiology
  • Guanosine Triphosphate / metabolism
  • Guanosine Triphosphate / physiology*
  • Humans
  • Hydrolysis
  • Mice
  • Mutagenesis, Site-Directed
  • Neurons / enzymology
  • Protein Glutamine gamma Glutamyltransferase 2
  • Time Factors
  • Transfection
  • Transglutaminases / isolation & purification
  • Transglutaminases / metabolism*
  • Transglutaminases / physiology

Substances

  • Guanosine Triphosphate
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins