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2022-11-14

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cc-by (c) Marquina, Maribel et al., 2022
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/194210

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

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Recurs relacionat

https://doi.org/10.1038/s41598-022-23970-8

Resum

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.

Matèries

Expressió gènica, Regulació genètica, Proteïnes quinases, Fosforilació

Matèries (anglès)

Gene expression, Genetic regulation, Protein kinases, Phosphorylation

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Articles publicats en revistes (Biomedicina)

Citació

MARQUINA, Maribel, et al. A new negative feedback mechanism for MAPK pathway inactivation through Srk1 MAPKAP kinase. Scientific Reports. 2022. Vol. 12, num. 1, pags. 19501. ISSN 2045-2322. [consulted: 11 of June of 2026]. Available at: https://hdl.handle.net/2445/194210

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