Negative feedback-loop mechanisms regulating HOG- and pheromone-MAPK signaling in yeast
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REVIEW
Negative feedback‑loop mechanisms regulating HOG‑ and pheromone‑MAPK signaling in yeast Araceli Vázquez‑Ibarra1 · Griselda Rodríguez‑Martínez1 · Gehenna Guerrero‑Serrano2 · Laura Kawasaki1 · Laura Ongay‑Larios3 · Roberto Coria1 Received: 27 April 2020 / Revised: 8 June 2020 / Accepted: 10 June 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract The pheromone response and the high osmolarity glycerol (HOG) pathways are considered the prototypical MAPK signaling systems. They are the best-understood pathways in eukaryotic cells, yet they continue to provide insights in how cells relate with the environment. These systems are subjected to tight regulatory circuits to prevent hyperactivation in length and intensity. Failure to do this may be a matter of life or death specially for unicellular organisms such as Saccharomyces cerevisiae. The signaling pathways are fine-tuned by positive and negative feedback loops exerted by pivotal control elements that allow precise responses to specific stimuli, despite the fact that some elements of the systems are common to different signaling pathways. Here we describe the experimentally proven negative feedback loops that modulate the pheromone response and the HOG pathways. As described in this review, MAP kinases are central mechanistic components of these feedback loops. They have the capacity to modulate basal signaling activity, a fast extranuclear response, and a longer-lasting transcriptional process. Keywords Hyperosmotic stress · Mating · G protein · Phosphorelay · Adaptation
Introduction Living cells respond to external and internal stressful conditions by adapting their metabolism to regain homeostasis. To achieve accurate responses, cells have evolved complex signaling pathways that regulate gene expression and metabolic processes. The most common signaling systems are composed of mitogen-activated protein kinase (MAPK) modules. The signal induced by the stimulus is transmitted by the sequential phosphorylation of a basic array of three Communicated by M. Kupiec. * Roberto Coria [email protected] 1
Departamento de Genética Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, México
2
Institut Curie, PSL Research University, CNRS UMR 144, 75005 Paris, France
3
Unidad de Biología Molecular, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, 04510 México City, México
proteins. Upon activation, a MAPKKK (or MEKK) phosphorylates conserved Ser and Thr residues located at the activation loop of its MAPKK (or MEK) target protein. The phosphorylated MAPKK then phosphorylates Thr and Tyr residues located in the activation loop of its target MAPK (or ERK). Finally, the MAPK phosphorylates various protein substrates to transmit the input signal. The cellular response depends on several properties of the stimulus such as its nature, its duration, its frequency, and its concentration. Thus, the signaling pathways are designed not only to interpret the presence
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