A Novel Serine/Threonine-Specific Protein Phosphotransferase Activity of Nm23/Nucleoside-Diphosphate Kinase
| العنوان: | A Novel Serine/Threonine-Specific Protein Phosphotransferase Activity of Nm23/Nucleoside-Diphosphate Kinase |
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| المؤلفون: | Matthias Engel, Michel Véron, Birgit Theisinger, Thomas Seib, Marie-Lise Lacombe, Steven Dooley, Cornelius Welter |
| المصدر: | European Journal of Biochemistry. 234:200-207 |
| بيانات النشر: | Wiley, 1995. |
| سنة النشر: | 1995 |
| مصطلحات موضوعية: | Threonine, Binding Sites, Kinase, Phosphotransferases, NM23 Nucleoside Diphosphate Kinases, Biology, Biochemistry, Nucleoside-diphosphate kinase, Serine, Phosphotransferase, Kinetics, Nucleoside-Diphosphate Kinase, Phosphoprotein, Tumor Cells, Cultured, Humans, Urea, Phosphorylation, Amino Acids, Protein kinase A, Monomeric GTP-Binding Proteins, Transcription Factors |
| الوصف: | Two human nm23 genes have been identified, designated nm23-H1 and nm23-H2, which encode the 88% identical nucleoside-diphosphate kinase (NDPK) A and NDPK B polypeptides, respectively. The nm23-H1 gene product has been shown to play a functional role in the suppression of tumor metastasis. The Nm23 proteins/NDPK are highly conserved throughout evolution and are implicated in controlling cellular differentiation and development in various species, while the underlying mechanisms remain undefined. Neither the NDPK activity nor the DNA-binding activity, identified recently for NDPK B, can satisfactory explain the regulatory functions of Nm23. The present study provides evidence that purified Nm23 proteins are capable of transferring a phosphate group to other proteins when non-denaturing amounts of urea are present. This novel Nm23/NDPK activity was found to be specific for serine and threonine residues, and the transphosphorylation of substrate proteins occurred stoichiometrically. Because of the absence of a substrate turn-over, the novel function was termed protein phosphotransferase activity instead of protein kinase activity. It is demonstrated that urea stimulates the interaction of NDPK with other proteins. Identical phosphoprotein patterns were obtained using purified NDPK preparations from human, Drosophila, yeast and Dictyostelium in the presence of urea. Partially purified NDPK from human erythrocytes produced a similar phosphorylation pattern independent of urea addition and also acted stoichiometrically. In this preparation, a protein phosphotransferase activity of Nm23 species may possibly be generated and/or stabilized by the interaction with copurified proteins. Using different mutants of Dictyostelium NDPK it was shown that the protein phosphotransferase activity depends on the same active site as the NDPK activity. A phosphotransfer mechanism analogous to that of protein-histidine kinases is proposed, involving a high-energy phosphohistidine intermediate. Furthermore, the novel Nm23 function is compared with an apparently similar protein phosphotransferase activity which was observed previously with partially purified NDPK from different plant species. |
| تدمد: | 1432-1033 0014-2956 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::43355c9839d6c737bfc67134ad1c16baTest https://doi.org/10.1111/j.1432-1033.1995.200_c.xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....43355c9839d6c737bfc67134ad1c16ba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14321033 00142956 |
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