Jeon Ju-Hong, Cho Sung-Yup, Kim Chai-Wan, Shin Dong-Myung, Kweon Joon-Chul, Choi Kyung-Ho, Park Sang-Chul, Kim In-Gyu
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, 28 Yongon Dong, Chongno Gu, Republic of Korea.
Biochem Biophys Res Commun. 2002 Jun 21;294(4):818-22. 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.
转谷氨酰胺酶2(TGase 2)是一种双功能酶,可催化钙依赖性转酰胺作用以及GTP结合/水解。转酰胺活性被认为与多种神经退行性疾病有关,如阿尔茨海默病和亨廷顿病。然而,TGase 2导致神经退行性变的调控机制尚不清楚。在本研究中,我们发现TGase 2的两种活性具有不同的稳定性;转酰胺活性比GTP水解活性更不稳定,并且GTP是稳定和展现转酰胺活性所必需的。此外,在转染实验中,TGase 2的GTP结合缺陷突变体未表现出任何转酰胺活性。这些结果表明,GTP结合对于TGase 2的转酰胺活性至关重要,这表明TGase 2介导的蛋白质交联可能与G蛋白偶联受体信号系统有关。因此,我们的数据有助于理解TGase 2活性的调控以及与TGase 2相关的发病机制。