Critical and synergy nodes in insulin-EGF signaling network
Signaling pathways are not isolated from their surroundings. They are also intervened by other signaling pathways known as “crosstalk mechanism”. One of the most important crosstalk mechanisms is the insulinEGF network. Although insulin and epidermal growth factor (EGF) networks have some complexity...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Ferdowsi University of Mashhad
2012-06-01
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| Series: | Journal of Cell and Molecular Research |
| Subjects: | |
| Online Access: | https://jcmr.um.ac.ir/article_26446_31425d7c6e8e31d640a91689a1a84330.pdf |
| _version_ | 1818976084882882560 |
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| author | Hassan Monhemia Mohammad Reza Hosseindokht Mohammareza Bozorgmehr Ahmad Reza Bahrami |
| author_facet | Hassan Monhemia Mohammad Reza Hosseindokht Mohammareza Bozorgmehr Ahmad Reza Bahrami |
| author_sort | Hassan Monhemia |
| collection | DOAJ |
| description | Signaling pathways are not isolated from their surroundings. They are also intervened by other signaling pathways known as “crosstalk mechanism”. One of the most important crosstalk mechanisms is the insulinEGF network. Although insulin and epidermal growth factor (EGF) networks have some complexity in their isolated forms, their complexities will grow in the crosstalk network. In this study, we used the analytical tools of the systems biology workbench for elucidating some ambiguities of the insulin-EGF crosstalk. Based on sensitivity analysis, we reconstructed an elucidated model with 51 chemical reactions in comparison with the previous model with 111 chemical reactions. Interestingly, this reduced model reproduces the results of the original model in synergy conditions. We noticed two controlling pathways with direct participation of phosphorylated insulin and EGF receptors that involve Insulin Receptor Substrate (IRS) and Src kinase modules. Also, insulin pathway by producing phosphatidylinositol-3, 4, 5-triphosphate (PIP3), and EGF pathway by activation of GAB1, control the downstream events and lead to potentialities in the mitogenic signal. Surprisingly, Shc and phosphatase SHP2-dependent reactions have no significant roles in the synergy conditions and are not involved in the reduced model. Regarding sensitivity analysis, all Ras/ERK cascade reactions are crucial for signal transduction and were kept in the reduced model. |
| first_indexed | 2024-12-20T16:06:14Z |
| format | Article |
| id | doaj.art-8dcbbddc1c2f489ab7cc80860bfee2fd |
| institution | Directory Open Access Journal |
| issn | 2008-9147 2717-3364 |
| language | English |
| last_indexed | 2024-12-20T16:06:14Z |
| publishDate | 2012-06-01 |
| publisher | Ferdowsi University of Mashhad |
| record_format | Article |
| series | Journal of Cell and Molecular Research |
| spelling | doaj.art-8dcbbddc1c2f489ab7cc80860bfee2fd2022-12-21T19:34:08ZengFerdowsi University of MashhadJournal of Cell and Molecular Research2008-91472717-33642012-06-0141182710.22067/jcmr.v4i1.1064226446Critical and synergy nodes in insulin-EGF signaling networkHassan MonhemiaMohammad Reza HosseindokhtMohammareza BozorgmehrAhmad Reza BahramiSignaling pathways are not isolated from their surroundings. They are also intervened by other signaling pathways known as “crosstalk mechanism”. One of the most important crosstalk mechanisms is the insulinEGF network. Although insulin and epidermal growth factor (EGF) networks have some complexity in their isolated forms, their complexities will grow in the crosstalk network. In this study, we used the analytical tools of the systems biology workbench for elucidating some ambiguities of the insulin-EGF crosstalk. Based on sensitivity analysis, we reconstructed an elucidated model with 51 chemical reactions in comparison with the previous model with 111 chemical reactions. Interestingly, this reduced model reproduces the results of the original model in synergy conditions. We noticed two controlling pathways with direct participation of phosphorylated insulin and EGF receptors that involve Insulin Receptor Substrate (IRS) and Src kinase modules. Also, insulin pathway by producing phosphatidylinositol-3, 4, 5-triphosphate (PIP3), and EGF pathway by activation of GAB1, control the downstream events and lead to potentialities in the mitogenic signal. Surprisingly, Shc and phosphatase SHP2-dependent reactions have no significant roles in the synergy conditions and are not involved in the reduced model. Regarding sensitivity analysis, all Ras/ERK cascade reactions are crucial for signal transduction and were kept in the reduced model.https://jcmr.um.ac.ir/article_26446_31425d7c6e8e31d640a91689a1a84330.pdfsignaling pathwayscrosstalkcomputational modelingsystems biology, insulin-egf networks, sensitivity analysis, targeted drug therapy |
| spellingShingle | Hassan Monhemia Mohammad Reza Hosseindokht Mohammareza Bozorgmehr Ahmad Reza Bahrami Critical and synergy nodes in insulin-EGF signaling network Journal of Cell and Molecular Research signaling pathways crosstalk computational modeling systems biology, insulin-egf networks, sensitivity analysis, targeted drug therapy |
| title | Critical and synergy nodes in insulin-EGF signaling network |
| title_full | Critical and synergy nodes in insulin-EGF signaling network |
| title_fullStr | Critical and synergy nodes in insulin-EGF signaling network |
| title_full_unstemmed | Critical and synergy nodes in insulin-EGF signaling network |
| title_short | Critical and synergy nodes in insulin-EGF signaling network |
| title_sort | critical and synergy nodes in insulin egf signaling network |
| topic | signaling pathways crosstalk computational modeling systems biology, insulin-egf networks, sensitivity analysis, targeted drug therapy |
| url | https://jcmr.um.ac.ir/article_26446_31425d7c6e8e31d640a91689a1a84330.pdf |
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