Mitogen-Activated Protein Kinase Kinase 5 Regulates Proliferation and Biosynthetic Processes in Procyclic Forms of Trypanosoma brucei
| Autor: | Elizabeth Sousa da Cunha, Sara Zanivan, Lisa J. Neilson, Carla V. de Paula Lima, Fabricio K Marchini, Marco Aurélio Krieger, Michel Batista, Lyris M. F. de Godoy, Fernanda G. Kugeratski |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Trypanosoma brucei brucei Trypanosoma brucei Mitogen-activated protein kinase kinase MAP Kinase Kinase 5 Biochemistry Mass Spectrometry MAP2K7 03 medical and health sciences ASK1 c-Raf Gene Silencing Protein kinase A Cell Proliferation 030102 biochemistry & molecular biology biology Cyclin-dependent kinase 2 Fatty Acids General Chemistry biology.organism_classification Protein kinase R Cell biology 030104 developmental biology Protein Biosynthesis biology.protein Energy Metabolism |
| Zdroj: | Journal of proteome research. 17(1) |
| ISSN: | 1535-3907 1535-3893 |
| Popis: | The pathogenic protozoan T. brucei alternates into distinct developmental stages in the mammalian and insect hosts. The mitogen-activated protein kinase (MAPK) signaling pathways transduce extracellular stimuli into a range of cellular responses, which ultimately lead to the adaptation to the external environment. Here, we combined a loss of function approach with stable isotope labeling with amino acids in cell culture (SILAC)-based mass spectrometry (MS) to investigate the role of the mitogen-activated protein kinase kinase 5 (MKK5) in T. brucei. The silencing of MKK5 significantly decreased the proliferation of procyclic forms of T. brucei. To shed light on the molecular alterations associated with this phenotype, we measured the total proteome and phosphoproteome of cells silenced for MKK5. In the total proteome, we observed a general decrease in proteins related to ribosome and translation as well as down-regulation of several components of the fatty acids biosynthesis pathway. In addition, we observed alterations in the protein levels and phosphorylation of key metabolic enzymes, which point toward a suppression of the oxidative metabolism. Taken together, our findings show that the silencing of MKK5 alters cell growth, energy metabolism, protein and fatty acids biosynthesis in procyclic T. brucei. |
| Databáze: | OpenAIRE |
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