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

• Published in: Biochemical and biophysical research communications 2002-06, Vol.294 (4), p.818-822
• Main Authors: Jeon, Ju-Hong, Cho, Sung-Yup, Kim, Chai-Wan, Shin, Dong-Myung, Kweon, Joon-Chul, Choi, Kyung-Ho, Park, Sang-Chul, Kim, In-Gyu
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Animals; Enzyme stability; Erythrocytes - enzymology; GTP binding/hydrolysis; 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; Time Factors; Transamidation; Transfection; Transglutaminase 2; Transglutaminases - isolation & purification; Transglutaminases - metabolism; Transglutaminases - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/S0006-291X(02)00582-X

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.