Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues

Abstract Ras is a plasma membrane (PM)-associated signaling hub protein that interacts with its partners (effectors) in a mutually exclusive fashion. We have shown earlier that competition for binding and hence the occurrence of specific binding events at a hub protein can modulate the activation of...

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Autores principales:	Simona Catozzi, Melinda Halasz, Christina Kiel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/80592e1be5ed4696a9e4b6bddc152edd
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spelling	oai:doaj.org-article:80592e1be5ed4696a9e4b6bddc152edd2021-12-02T13:30:11ZPredicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues10.1038/s41540-021-00170-02056-7189https://doaj.org/article/80592e1be5ed4696a9e4b6bddc152edd2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41540-021-00170-0https://doaj.org/toc/2056-7189Abstract Ras is a plasma membrane (PM)-associated signaling hub protein that interacts with its partners (effectors) in a mutually exclusive fashion. We have shown earlier that competition for binding and hence the occurrence of specific binding events at a hub protein can modulate the activation of downstream pathways. Here, using a mechanistic modeling approach that incorporates high-quality proteomic data of Ras and 56 effectors in 29 (healthy) human tissues, we quantified the amount of individual Ras-effector complexes, and characterized the (stationary) Ras “wiring landscape” specific to each tissue. We identified nine effectors that are in significant amount in complex with Ras in at least one of the 29 tissues. We simulated both mutant- and stimulus-induced network re-configurations, and assessed their divergence from the reference scenario, specifically discussing a case study for two stimuli in three epithelial tissues. These analyses pointed to 32 effectors that are in significant amount in complex with Ras only if they are additionally recruited to the PM, e.g. via membrane-binding domains or domains binding to activated receptors at the PM. Altogether, our data emphasize the importance of tissue context for binding events at the Ras signaling hub.Simona CatozziMelinda HalaszChristina KielNature PortfolioarticleBiology (General)QH301-705.5ENnpj Systems Biology and Applications, Vol 7, Iss 1, Pp 1-15 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Simona Catozzi Melinda Halasz Christina Kiel Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
description	Abstract Ras is a plasma membrane (PM)-associated signaling hub protein that interacts with its partners (effectors) in a mutually exclusive fashion. We have shown earlier that competition for binding and hence the occurrence of specific binding events at a hub protein can modulate the activation of downstream pathways. Here, using a mechanistic modeling approach that incorporates high-quality proteomic data of Ras and 56 effectors in 29 (healthy) human tissues, we quantified the amount of individual Ras-effector complexes, and characterized the (stationary) Ras “wiring landscape” specific to each tissue. We identified nine effectors that are in significant amount in complex with Ras in at least one of the 29 tissues. We simulated both mutant- and stimulus-induced network re-configurations, and assessed their divergence from the reference scenario, specifically discussing a case study for two stimuli in three epithelial tissues. These analyses pointed to 32 effectors that are in significant amount in complex with Ras only if they are additionally recruited to the PM, e.g. via membrane-binding domains or domains binding to activated receptors at the PM. Altogether, our data emphasize the importance of tissue context for binding events at the Ras signaling hub.
format	article
author	Simona Catozzi Melinda Halasz Christina Kiel
author_facet	Simona Catozzi Melinda Halasz Christina Kiel
author_sort	Simona Catozzi
title	Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
title_short	Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
title_full	Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
title_fullStr	Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
title_full_unstemmed	Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues
title_sort	predicted ‘wiring landscape’ of ras-effector interactions in 29 human tissues
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/80592e1be5ed4696a9e4b6bddc152edd
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Predicted ‘wiring landscape’ of Ras-effector interactions in 29 human tissues

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