Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast
The phosphorylation and dephosphorylation of proteins by kinases and phosphatases constitute an essential regulatory network in eukaryotic cells. This network supports the flow of information from sensors through signaling systems to effector molecules, and ultimately drives the phenotype and functi...
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2010
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19450877_v3_n153_p_Bodenmiller http://hdl.handle.net/20.500.12110/paper_19450877_v3_n153_p_Bodenmiller |
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paper:paper_19450877_v3_n153_p_Bodenmiller2023-06-08T16:32:29Z Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast phosphatase phosphoprotein protein kinase phosphatase phosphoprotein phosphotransferase article cell growth controlled study enzyme activation hemostasis in vivo study nonhuman phenotype priority journal protein analysis protein phosphorylation proteomics Saccharomyces cerevisiae signal transduction Bayes theorem biological model comparative study gene deletion genetics liquid chromatography metabolism methodology phosphorylation physiology Saccharomyces cerevisiae signal transduction species difference tandem mass spectrometry Eukaryota Saccharomyces cerevisiae Bayes Theorem Chromatography, Liquid Gene Deletion Metabolic Networks and Pathways Models, Biological Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Proteomics Saccharomyces cerevisiae Signal Transduction Species Specificity Tandem Mass Spectrometry The phosphorylation and dephosphorylation of proteins by kinases and phosphatases constitute an essential regulatory network in eukaryotic cells. This network supports the flow of information from sensors through signaling systems to effector molecules, and ultimately drives the phenotype and function of cells, tissues, and organisms. Dysregulation of this process has severe consequencesand is one of the main factors in the emergence and progression of diseases, including cancer. Thus, major efforts have been invested in developing specific inhibitors that modulate the activity of individual kinases or phosphatases; however, it has been difficult to assess how such pharmacological interventions would affect the cellular signaling network as a whole. Here, we used label-free, quantitative phosphoproteomics in a systematically perturbed model organism (Saccharomyces cerevisiae) to determine the relationships between 97 kinases, 27 phosphatases, and more than 1000 phosphoproteins. We identified 8814 regulated phosphorylation events, describing the first system-wide protein phosphorylation network in vivo. Our results show that, at steady state, inactivation of most kinases and phosphatases affected large parts of the phosphorylation-modulated signal transduction machinery, and not only the immediate downstream targets. The observed cellular growth phenotype was often well maintained despite the perturbations, arguing for considerable robustness in the system. Our results serve to constrain future models of cellular signaling and reinforce the idea that simple linear representations of signaling pathways might be insufficient for drug development and for describing organismal homeostasis. © 2008 American Association for the Advancement of Science. 2010 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19450877_v3_n153_p_Bodenmiller http://hdl.handle.net/20.500.12110/paper_19450877_v3_n153_p_Bodenmiller |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
phosphatase phosphoprotein protein kinase phosphatase phosphoprotein phosphotransferase article cell growth controlled study enzyme activation hemostasis in vivo study nonhuman phenotype priority journal protein analysis protein phosphorylation proteomics Saccharomyces cerevisiae signal transduction Bayes theorem biological model comparative study gene deletion genetics liquid chromatography metabolism methodology phosphorylation physiology Saccharomyces cerevisiae signal transduction species difference tandem mass spectrometry Eukaryota Saccharomyces cerevisiae Bayes Theorem Chromatography, Liquid Gene Deletion Metabolic Networks and Pathways Models, Biological Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Proteomics Saccharomyces cerevisiae Signal Transduction Species Specificity Tandem Mass Spectrometry |
| spellingShingle |
phosphatase phosphoprotein protein kinase phosphatase phosphoprotein phosphotransferase article cell growth controlled study enzyme activation hemostasis in vivo study nonhuman phenotype priority journal protein analysis protein phosphorylation proteomics Saccharomyces cerevisiae signal transduction Bayes theorem biological model comparative study gene deletion genetics liquid chromatography metabolism methodology phosphorylation physiology Saccharomyces cerevisiae signal transduction species difference tandem mass spectrometry Eukaryota Saccharomyces cerevisiae Bayes Theorem Chromatography, Liquid Gene Deletion Metabolic Networks and Pathways Models, Biological Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Proteomics Saccharomyces cerevisiae Signal Transduction Species Specificity Tandem Mass Spectrometry Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| topic_facet |
phosphatase phosphoprotein protein kinase phosphatase phosphoprotein phosphotransferase article cell growth controlled study enzyme activation hemostasis in vivo study nonhuman phenotype priority journal protein analysis protein phosphorylation proteomics Saccharomyces cerevisiae signal transduction Bayes theorem biological model comparative study gene deletion genetics liquid chromatography metabolism methodology phosphorylation physiology Saccharomyces cerevisiae signal transduction species difference tandem mass spectrometry Eukaryota Saccharomyces cerevisiae Bayes Theorem Chromatography, Liquid Gene Deletion Metabolic Networks and Pathways Models, Biological Phosphoproteins Phosphoric Monoester Hydrolases Phosphorylation Phosphotransferases Proteomics Saccharomyces cerevisiae Signal Transduction Species Specificity Tandem Mass Spectrometry |
| description |
The phosphorylation and dephosphorylation of proteins by kinases and phosphatases constitute an essential regulatory network in eukaryotic cells. This network supports the flow of information from sensors through signaling systems to effector molecules, and ultimately drives the phenotype and function of cells, tissues, and organisms. Dysregulation of this process has severe consequencesand is one of the main factors in the emergence and progression of diseases, including cancer. Thus, major efforts have been invested in developing specific inhibitors that modulate the activity of individual kinases or phosphatases; however, it has been difficult to assess how such pharmacological interventions would affect the cellular signaling network as a whole. Here, we used label-free, quantitative phosphoproteomics in a systematically perturbed model organism (Saccharomyces cerevisiae) to determine the relationships between 97 kinases, 27 phosphatases, and more than 1000 phosphoproteins. We identified 8814 regulated phosphorylation events, describing the first system-wide protein phosphorylation network in vivo. Our results show that, at steady state, inactivation of most kinases and phosphatases affected large parts of the phosphorylation-modulated signal transduction machinery, and not only the immediate downstream targets. The observed cellular growth phenotype was often well maintained despite the perturbations, arguing for considerable robustness in the system. Our results serve to constrain future models of cellular signaling and reinforce the idea that simple linear representations of signaling pathways might be insufficient for drug development and for describing organismal homeostasis. © 2008 American Association for the Advancement of Science. |
| title |
Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| title_short |
Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| title_full |
Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| title_fullStr |
Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| title_full_unstemmed |
Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| title_sort |
phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast |
| publishDate |
2010 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_19450877_v3_n153_p_Bodenmiller http://hdl.handle.net/20.500.12110/paper_19450877_v3_n153_p_Bodenmiller |
| _version_ |
1768546274196324352 |