A systems model of phosphorylation for inflammatory signaling events.
Phosphorylation is a fundamental biochemical reaction that modulates protein activity in cells. While a single phosphorylation event is relatively easy to understand, multisite phosphorylation requires systems approaches for deeper elucidation of the underlying molecular mechanisms. In this paper we...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC4205014?pdf=render |
| _version_ | 1818925007431008256 |
|---|---|
| author | Ildar I Sadreev Michael Z Q Chen Gavin I Welsh Yoshinori Umezawa Nikolay V Kotov Najl V Valeyev |
| author_facet | Ildar I Sadreev Michael Z Q Chen Gavin I Welsh Yoshinori Umezawa Nikolay V Kotov Najl V Valeyev |
| author_sort | Ildar I Sadreev |
| collection | DOAJ |
| description | Phosphorylation is a fundamental biochemical reaction that modulates protein activity in cells. While a single phosphorylation event is relatively easy to understand, multisite phosphorylation requires systems approaches for deeper elucidation of the underlying molecular mechanisms. In this paper we develop a mechanistic model for single- and multi-site phosphorylation. The proposed model is compared with previously reported studies. We compare the predictions of our model with experiments published in the literature in the context of inflammatory signaling events in order to provide a mechanistic description of the multisite phosphorylation-mediated regulation of Signal Transducer and Activator of Transcription 3 (STAT3) and Interferon Regulatory Factor 5 (IRF-5) proteins. The presented model makes crucial predictions for transcription factor phosphorylation events in the immune system. The model proposes potential mechanisms for T cell phenotype switching and production of cytokines. This study also provides a generic framework for the better understanding of a large number of multisite phosphorylation-regulated biochemical circuits. |
| first_indexed | 2024-12-20T02:34:23Z |
| format | Article |
| id | doaj.art-68e1047dbde04b55b1d0d1209bc1cd8c |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-20T02:34:23Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-68e1047dbde04b55b1d0d1209bc1cd8c2022-12-21T19:56:29ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01910e11091310.1371/journal.pone.0110913A systems model of phosphorylation for inflammatory signaling events.Ildar I SadreevMichael Z Q ChenGavin I WelshYoshinori UmezawaNikolay V KotovNajl V ValeyevPhosphorylation is a fundamental biochemical reaction that modulates protein activity in cells. While a single phosphorylation event is relatively easy to understand, multisite phosphorylation requires systems approaches for deeper elucidation of the underlying molecular mechanisms. In this paper we develop a mechanistic model for single- and multi-site phosphorylation. The proposed model is compared with previously reported studies. We compare the predictions of our model with experiments published in the literature in the context of inflammatory signaling events in order to provide a mechanistic description of the multisite phosphorylation-mediated regulation of Signal Transducer and Activator of Transcription 3 (STAT3) and Interferon Regulatory Factor 5 (IRF-5) proteins. The presented model makes crucial predictions for transcription factor phosphorylation events in the immune system. The model proposes potential mechanisms for T cell phenotype switching and production of cytokines. This study also provides a generic framework for the better understanding of a large number of multisite phosphorylation-regulated biochemical circuits.http://europepmc.org/articles/PMC4205014?pdf=render |
| spellingShingle | Ildar I Sadreev Michael Z Q Chen Gavin I Welsh Yoshinori Umezawa Nikolay V Kotov Najl V Valeyev A systems model of phosphorylation for inflammatory signaling events. PLoS ONE |
| title | A systems model of phosphorylation for inflammatory signaling events. |
| title_full | A systems model of phosphorylation for inflammatory signaling events. |
| title_fullStr | A systems model of phosphorylation for inflammatory signaling events. |
| title_full_unstemmed | A systems model of phosphorylation for inflammatory signaling events. |
| title_short | A systems model of phosphorylation for inflammatory signaling events. |
| title_sort | systems model of phosphorylation for inflammatory signaling events |
| url | http://europepmc.org/articles/PMC4205014?pdf=render |
| work_keys_str_mv | AT ildarisadreev asystemsmodelofphosphorylationforinflammatorysignalingevents AT michaelzqchen asystemsmodelofphosphorylationforinflammatorysignalingevents AT gaviniwelsh asystemsmodelofphosphorylationforinflammatorysignalingevents AT yoshinoriumezawa asystemsmodelofphosphorylationforinflammatorysignalingevents AT nikolayvkotov asystemsmodelofphosphorylationforinflammatorysignalingevents AT najlvvaleyev asystemsmodelofphosphorylationforinflammatorysignalingevents AT ildarisadreev systemsmodelofphosphorylationforinflammatorysignalingevents AT michaelzqchen systemsmodelofphosphorylationforinflammatorysignalingevents AT gaviniwelsh systemsmodelofphosphorylationforinflammatorysignalingevents AT yoshinoriumezawa systemsmodelofphosphorylationforinflammatorysignalingevents AT nikolayvkotov systemsmodelofphosphorylationforinflammatorysignalingevents AT najlvvaleyev systemsmodelofphosphorylationforinflammatorysignalingevents |