Plasticity of the MAPK signaling network in response to mechanical stress.

Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilita...

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Autores principales:	Andrea M Pereira, Cicerone Tudor, Philippe-Alexandre Pouille, Shashank Shekhar, Johannes S Kanger, Vinod Subramaniam, Enrique Martín-Blanco
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/185f4056751e4bdd892d64f1a3b359e2
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spelling	oai:doaj.org-article:185f4056751e4bdd892d64f1a3b359e22021-11-25T06:08:29ZPlasticity of the MAPK signaling network in response to mechanical stress.1932-620310.1371/journal.pone.0101963https://doaj.org/article/185f4056751e4bdd892d64f1a3b359e22014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/25025279/?tool=EBIhttps://doaj.org/toc/1932-6203Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.Andrea M PereiraCicerone TudorPhilippe-Alexandre PouilleShashank ShekharJohannes S KangerVinod SubramaniamEnrique Martín-BlancoPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 7, p e101963 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andrea M Pereira Cicerone Tudor Philippe-Alexandre Pouille Shashank Shekhar Johannes S Kanger Vinod Subramaniam Enrique Martín-Blanco Plasticity of the MAPK signaling network in response to mechanical stress.
description	Cells display versatile responses to mechanical inputs and recent studies have identified the mitogen-activated protein kinase (MAPK) cascades mediating the biological effects observed upon mechanical stimulation. Although, MAPK pathways can act insulated from each other, several mechanisms facilitate the crosstalk between the components of these cascades. Yet, the combinatorial complexity of potential molecular interactions between these elements have prevented the understanding of their concerted functions. To analyze the plasticity of the MAPK signaling network in response to mechanical stress we performed a non-saturating epistatic screen in resting and stretched conditions employing as readout a JNK responsive dJun-FRET biosensor. By knocking down MAPKs, and JNK pathway regulators, singly or in pairs in Drosophila S2R+ cells, we have uncovered unexpected regulatory links between JNK cascade kinases, Rho GTPases, MAPKs and the JNK phosphatase Puc. These relationships have been integrated in a system network model at equilibrium accounting for all experimentally validated interactions. This model allows predicting the global reaction of the network to its modulation in response to mechanical stress. It also highlights its context-dependent sensitivity.
format	article
author	Andrea M Pereira Cicerone Tudor Philippe-Alexandre Pouille Shashank Shekhar Johannes S Kanger Vinod Subramaniam Enrique Martín-Blanco
author_facet	Andrea M Pereira Cicerone Tudor Philippe-Alexandre Pouille Shashank Shekhar Johannes S Kanger Vinod Subramaniam Enrique Martín-Blanco
author_sort	Andrea M Pereira
title	Plasticity of the MAPK signaling network in response to mechanical stress.
title_short	Plasticity of the MAPK signaling network in response to mechanical stress.
title_full	Plasticity of the MAPK signaling network in response to mechanical stress.
title_fullStr	Plasticity of the MAPK signaling network in response to mechanical stress.
title_full_unstemmed	Plasticity of the MAPK signaling network in response to mechanical stress.
title_sort	plasticity of the mapk signaling network in response to mechanical stress.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/185f4056751e4bdd892d64f1a3b359e2
work_keys_str_mv	AT andreampereira plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT ciceronetudor plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT philippealexandrepouille plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT shashankshekhar plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT johannesskanger plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT vinodsubramaniam plasticityofthemapksignalingnetworkinresponsetomechanicalstress AT enriquemartinblanco plasticityofthemapksignalingnetworkinresponsetomechanicalstress
_version_	1718414089798025216

Plasticity of the MAPK signaling network in response to mechanical stress.

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