A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase

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  • dc.contributor.author Marquina, Maribel
  • dc.contributor.author Lambea, Eva
  • dc.contributor.author Carmona, Mercè
  • dc.contributor.author Sánchez-Marinas, Marta
  • dc.contributor.author López-Aviles, Sandra
  • dc.contributor.author Ayté del Olmo, José
  • dc.contributor.author Hidalgo Hernando, Elena
  • dc.contributor.author Aligué, Rosa
  • dc.date.accessioned 2022-12-20T07:01:50Z
  • dc.date.available 2022-12-20T07:01:50Z
  • dc.date.issued 2022
  • dc.description.abstract The fission yeast mitogen-activated kinase (MAPK) Sty1 is essential for cell survival in response to different environmental insults. In unstimulated cells, Sty1 forms an inactive ternary cytoplasmatic complex with the MAPKK Wis1 and the MAPKAP kinase Srk1. Wis1 phosphorylates and activates Sty1, inducing the nuclear translocation of the complex. Once in the nucleus, Sty1 phosphorylates and activates Srk1, which in turns inhibits Cdc25 and cell cycle progression, before being degraded in a proteasome-dependent manner. In parallel, active nuclear Sty1 activates the transcription factor Atf1, which results in the expression of stress response genes including pyp2 (a MAPK phosphatase) and srk1. Despite its essentiality in response to stress, persistent activation of the MAPK pathway can be deleterious and induces cell death. Thus, timely pathway inactivation is essential to ensure an appropriate response and cell viability. Here, uncover a role for the MAPKAP kinase Srk1 as an essential component of a negative feedback loop regulating the Sty1 pathway through phosphorylation and inhibition of the Wis1 MAPKK. This feedback regulation by a downstream kinase in the pathway highlights an additional mechanism for fine-tuning of MAPK signaling. Thus, our results indicate that Srk1 not only facilitates the adaptation to stress conditions by preventing cell cycle progression, but also plays an instrumental role regulating the upstream kinases in the stress MAPK pathway.
  • dc.description.sponsorship This work was supported by the Spanish Ministry of Economy and Competitiveness grant BFU2015-65311-R to RA and the UB-Fertinagro Biotech collaboration agreement RL000901.We thank La Caixa Foundation for the research agreement support and the institutional support of Government of Catalonia (grant SRG201 7-00037).
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Marquina M, Lambea E, Carmona M, Sánchez-Marinas M, López-Aviles S, Ayte J, Hidalgo E, Aligue R. A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase. Sci Rep. 2022 Nov 14;12(1):19501. DOI: 10.1038/s41598-022-23970-8
  • dc.identifier.doi http://dx.doi.org/10.1038/s41598-022-23970-8
  • dc.identifier.issn 2045-2322
  • dc.identifier.uri http://hdl.handle.net/10230/55175
  • dc.language.iso eng
  • dc.publisher Nature Research
  • dc.relation.ispartof Sci Rep. 2022 Nov 14;12(1):19501
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-65311-R
  • dc.rights © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by/4.0/
  • dc.subject.keyword Cell biology
  • dc.subject.keyword Molecular biology
  • dc.title A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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