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Targeting the Interaction between the SH3 Domain of Grb2 and Gab2
Gab2 is a scaffolding protein, overexpressed in many types of cancers, that plays a key role in the formation of signaling complexes involved in cellular proliferation, migration, and differentiation. The interaction between Gab2 and the C-terminal SH3 domain of the protein Grb2 is crucial for the a...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695167/ https://www.ncbi.nlm.nih.gov/pubmed/33171874 http://dx.doi.org/10.3390/cells9112435 |
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author | Malagrinò, Francesca Coluccia, Antonio Bufano, Marianna Regina, Giuseppe La Puxeddu, Michela Toto, Angelo Visconti, Lorenzo Paone, Alessio Magnifico, Maria Chiara Troilo, Francesca Cutruzzolà, Francesca Silvestri, Romano Gianni, Stefano |
author_facet | Malagrinò, Francesca Coluccia, Antonio Bufano, Marianna Regina, Giuseppe La Puxeddu, Michela Toto, Angelo Visconti, Lorenzo Paone, Alessio Magnifico, Maria Chiara Troilo, Francesca Cutruzzolà, Francesca Silvestri, Romano Gianni, Stefano |
author_sort | Malagrinò, Francesca |
collection | PubMed |
description | Gab2 is a scaffolding protein, overexpressed in many types of cancers, that plays a key role in the formation of signaling complexes involved in cellular proliferation, migration, and differentiation. The interaction between Gab2 and the C-terminal SH3 domain of the protein Grb2 is crucial for the activation of the proliferation-signaling pathway Ras/Erk, thus representing a potential pharmacological target. In this study, we identified, by virtual screening, seven potential inhibitor molecules that were experimentally tested through kinetic and equilibrium binding experiments. One compound showed a remarkable effect in lowering the affinity of the C-SH3 domain for Gab2. This inhibitory effect was subsequently validated in cellula by using lung cancer cell lines A549 and H1299. Our results are discussed under the light of previous works on the C-SH3:Gab2 interaction. |
format | Online Article Text |
id | pubmed-7695167 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-76951672020-11-28 Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 Malagrinò, Francesca Coluccia, Antonio Bufano, Marianna Regina, Giuseppe La Puxeddu, Michela Toto, Angelo Visconti, Lorenzo Paone, Alessio Magnifico, Maria Chiara Troilo, Francesca Cutruzzolà, Francesca Silvestri, Romano Gianni, Stefano Cells Article Gab2 is a scaffolding protein, overexpressed in many types of cancers, that plays a key role in the formation of signaling complexes involved in cellular proliferation, migration, and differentiation. The interaction between Gab2 and the C-terminal SH3 domain of the protein Grb2 is crucial for the activation of the proliferation-signaling pathway Ras/Erk, thus representing a potential pharmacological target. In this study, we identified, by virtual screening, seven potential inhibitor molecules that were experimentally tested through kinetic and equilibrium binding experiments. One compound showed a remarkable effect in lowering the affinity of the C-SH3 domain for Gab2. This inhibitory effect was subsequently validated in cellula by using lung cancer cell lines A549 and H1299. Our results are discussed under the light of previous works on the C-SH3:Gab2 interaction. MDPI 2020-11-07 /pmc/articles/PMC7695167/ /pubmed/33171874 http://dx.doi.org/10.3390/cells9112435 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Malagrinò, Francesca Coluccia, Antonio Bufano, Marianna Regina, Giuseppe La Puxeddu, Michela Toto, Angelo Visconti, Lorenzo Paone, Alessio Magnifico, Maria Chiara Troilo, Francesca Cutruzzolà, Francesca Silvestri, Romano Gianni, Stefano Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title | Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title_full | Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title_fullStr | Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title_full_unstemmed | Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title_short | Targeting the Interaction between the SH3 Domain of Grb2 and Gab2 |
title_sort | targeting the interaction between the sh3 domain of grb2 and gab2 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695167/ https://www.ncbi.nlm.nih.gov/pubmed/33171874 http://dx.doi.org/10.3390/cells9112435 |
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