A two-component system that regulates an osmosensing MAP kinase cascade in yeast

Maeda, Tatsuya; Wurgler-Murphy, Susannah M.; Saito, Haruo

doi:10.1038/369242a0

Cited by 1,052 publications

(1,061 citation statements)

References 25 publications

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“…Simulating the osmotic shock profile with a fourfold higher protein phosphatase level resulted in a similar period of HOG pathway activity but diminished amplitudes of Hog1P 2 and mRNA. Experimentally this was tested by overexpressing PTP2 from the GAL1 promoter 29 . The experimentally observed profile was similar to that obtained in simulations ( Supplementary Fig.…”

Section: Time Course Experimentsmentioning

confidence: 99%

Integrative model of the response of yeast to osmotic shock

et al. 2005

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Integration of experimental studies with mathematical modeling allows insight into systems properties, prediction of perturbation effects and generation of hypotheses for further research. We present a comprehensive mathematical description of the cellular response of yeast to hyperosmotic shock. The model integrates a biochemical reaction network comprising receptor stimulation, mitogen-activated protein kinase cascade dynamics, activation of gene expression and adaptation of cellular metabolism with a thermodynamic description of volume regulation and osmotic pressure. Simulations agree well with experimental results obtained under different stress conditions or with specific mutants. The model is predictive since it suggests previously unrecognized features of the system with respect to osmolyte accumulation and feedback control, as confirmed with experiments. The mathematical description presented is a valuable tool for future studies on osmoregulation in yeast and-with appropriate modifications-other organisms. It also serves as a starting point for a comprehensive description of cellular signaling.Osmoregulation encompasses active processes with which cells monitor and adjust osmotic pressure and control shape, turgor and relative water content. Even individual cells in multicellular organisms respond to osmotic changes, and strategies of cellular adaptation are conserved from bacteria to human 1 . The yeast Saccharomyces cerevisiae is a suitable model system to study osmoregulation and a substantial amount of information is available on osmotic shockinduced signal transduction, control of gene expression and accumulation of osmolytes 2 .Osmoregulation is a homeostatic process, though commonly studied as a response to osmotic shock. Central to yeast osmotic adaptation is the high osmolarity glycerol (HOG) signaling system 2,3 (Fig. 1). S. cerevisiae monitors osmotic changes through the plasma membrane-localized sensor histidine kinase Sln1. Under ambient conditions, Sln1 is active and inhibits signaling. Upon loss of turgor pressure, Sln1 is inactivated 4 resulting in activation of a mitogen-activated protein (MAP) kinase cascade and phosphorylation of the MAP kinase Hog1. Active Hog1 accumulates in the nucleus where it affects gene expression. Two HOG target genes encode enzymes in glycerol production. Hence, activation of Hog1 stimulates the production of glycerol, which serves as an osmolyte to increase intracellular osmotic pressure. Glycerol accumulation is also controlled by rapid closing of the aquaglyceroporin Fps1, which is an osmolarity-regulated glycerol channel. Hog1 activation and Hog1-dependent transcriptional stimulation are transient processes, indicating rigorous feedback control. Several protein phosphatases are known as negative regulators of the pathway. Although the overall organization of the systems is well characterized, open questions concern the mechanisms underlying activation and deactivation of the system, feedback control and the causal relationship between different events in...

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Section: Time Course Experimentsmentioning

confidence: 99%

Integrative model of the response of yeast to osmotic shock

et al. 2005

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“…Several members can efficiently dephosphorylate p38α and p38β [46,47]; however, p38γ and p38δ are resistant to all known MKP family members. In addition, other types of phosphatases such as serine/ threonine protein phosphotase type 2C (PP2C) has been shown to have a role in downregulating the MAP kinase HOG1 pathway as well as negatively regulating human MKK6 and MKK4 levels in vitro and in vivo [48][49][50][51]. Taken together, these results suggest a mechanism by which p38 isoforms are differentially regulated depending on phosphatase levels and specificity.…”

Section: Downregulation Of the P38 Signaling Pathwaymentioning

confidence: 99%

Activation and signaling of the p38 MAP kinase pathway

2005

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The family members of the mitogen-activated protein (MAP) kinases mediate a wide variety of cellular behaviors in response to extracellular stimuli. One of the four main sub-groups, the p38 group of MAP kinases, serve as a nexus for signal transduction and play a vital role in numerous biological processes. In this review, we highlight the known characteristics and components of the p38 pathway along with the mechanism and consequences of p38 activation. We focus on the role of p38 as a signal transduction mediator and examine the evidence linking p38 to inflammation, cell cycle, cell death, development, cell differentiation, senescence and tumorigenesis in specific cell types. Upstream and downstream components of p38 are described and questions remaining to be answered are posed. Finally, we propose several directions for future research on p38.

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“…However, unlike the situation in mammalian cells and in fission yeast, this pathway is only efficiently activated by osmotic stress, and appears to be relatively insensitive to other stress conditions (Brewster et al 1993;Schuller et al 1994). A series of elegant genetic studies identified a transmembrane histidine kinase, Sln1, as a sensor of external osmolarity (Maeda et al 1994). This sensor appears to connect the outer membrane with the HOG1 MAPK module by using a phospho-relay system which is similar to the two-component systems that commonly operate in bacteria.…”

Section: The Signal Transduction Pathwaysmentioning

confidence: 99%

Stress‐activated signalling pathways in yeast

1998

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Eukaryotic cells have developed response mechanisms to combat the harmful effects of a variety of stress conditions. In the majority of cases, such responses involve changes in the gene expression pattern of the cell, leading to increased levels and activities of proteins that have stress-protective functions. Over the last few years, considerable progress has been made in understanding how stress-dependent transcriptional changes are brought about, and it transpires that the underlying mechanisms are highly conserved, being similar in organisms ranging from yeast to man. Many of the stress signals derive from the extracellular environment and accordingly these signals require transduction from the cell surface to the nucleus. This is accomplished through stress-activated signalling pathways, key amongst which are the highly conserved stress-activated MAP kinase pathways. Stimulation of these pathways leads to the increased activity of specific transcription factors and consequently the increased expression of certain stress-related genes. In this review, we focus on the progress that has been made in understanding these stress responses in yeast.

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A two-component system that regulates an osmosensing MAP kinase cascade in yeast

Cited by 1,052 publications

References 25 publications

Integrative model of the response of yeast to osmotic shock

Integrative model of the response of yeast to osmotic shock

Activation and signaling of the p38 MAP kinase pathway

Stress‐activated signalling pathways in yeast

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