An Osmosensing Signal Transduction Pathway in Yeast

Brewster, Jay L.; Valoir, T de; Dwyer, ND; Winter, Edward; Gustin, MC

doi:10.1126/science.7681220

Cited by 1,179 publications

(1,028 citation statements)

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“…Phosphorylated Ssk2p then activates the MAPKK Pbs2p [38,40,41]. Activated Pbs2p can phosphorylate and activate Hog1p [42]. Among all these interactions observed by experiments, all were uncovered in the constructed subnetwork except for the Ypd1p-Ssk1p and Ssk1p-Ssk2p, which can be regarded as false negatives of the constructed subnetwork.…”

Section: Resultsmentioning

confidence: 99%

Integrated cellular network of transcription regulations and protein-protein interactions

Wang

Chen

2010

BMC Syst Biol

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BackgroundWith the accumulation of increasing omics data, a key goal of systems biology is to construct networks at different cellular levels to investigate cellular machinery of the cell. However, there is currently no satisfactory method to construct an integrated cellular network that combines the gene regulatory network and the signaling regulatory pathway.ResultsIn this study, we integrated different kinds of omics data and developed a systematic method to construct the integrated cellular network based on coupling dynamic models and statistical assessments. The proposed method was applied to S. cerevisiae stress responses, elucidating the stress response mechanism of the yeast. From the resulting integrated cellular network under hyperosmotic stress, the highly connected hubs which are functionally relevant to the stress response were identified. Beyond hyperosmotic stress, the integrated network under heat shock and oxidative stress were also constructed and the crosstalks of these networks were analyzed, specifying the significance of some transcription factors to serve as the decision-making devices at the center of the bow-tie structure and the crucial role for rapid adaptation scheme to respond to stress. In addition, the predictive power of the proposed method was also demonstrated.ConclusionsWe successfully construct the integrated cellular network which is validated by literature evidences. The integration of transcription regulations and protein-protein interactions gives more insight into the actual biological network and is more predictive than those without integration. The method is shown to be powerful and flexible and can be used under different conditions and for different species. The coupling dynamic models of the whole integrated cellular network are very useful for theoretical analyses and for further experiments in the fields of network biology and synthetic biology.

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Section: Resultsmentioning

confidence: 99%

Integrated cellular network of transcription regulations and protein-protein interactions

Wang

Chen

2010

BMC Syst Biol

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“…The MAP kinase Hog1 functions in another MAP kinase cascade required for proliferation in high-osmolarity media. Mutants lacking this kinase are defective in cytokinesis and show an aberrant morphology under conditions of high osmolarity (Brewster et al, 1993). We constructed an skm1 slt2 double mutant by crossing strains HM31 (skm1⌬::URA3) and DL455 (slt2⌬::TRP1) and selecting segregants bearing both mutations.…”

Section: Skm1p Does Not Interact Genetically With Other Morphogeneticmentioning

confidence: 99%

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

Martı́n

Mendoza

Rodrı́guez-Pachón

et al. 1997

Molecular Microbiology

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SummarySte20/PAK serine/threonine protein kinases have been suggested as playing essential roles in cell signalling and morphogenesis as potential targets of Cdc42 and Rac GTPases. We have isolated and characterized the Saccharomyces cerevisiae SKM1 gene, which codes for a novel member of this family of protein kinases. The amino acid sequence analysis of Skm1p revealed the presence of a PH domain and a putative p21-binding domain near its amino terminus, suggesting its involvement in cellular signalling or cytoskeletal functions. However, deletion of SKM1 produced no detectable phenotype under standard laboratory conditions. Moreover, disruption of each of the two other S. cerevisiae Ste20/PAK-like kinase-encoding genes, STE20 and CLA4, in skm1 backgrounds, showed that Skm1p is not redundant with Ste20p or Cla4p. Interestingly, overexpression of SKM1 led to morphological alterations, indicating a possible role for this protein in morphogenetic control. Furthermore, overproduction of Skm1p lacking its N-terminus caused growth arrest. This effect was also seen when similarly truncated versions of Ste20p or Cla4p were overexpressed. We further observed that overproduction of this C-terminal fragment of Skm1p complements the mating defect of a ste20 mutant strain. These results suggest that the N-terminal domains of S. cerevisiae Ste20/ PAK-like protein kinases share a negative regulatory function and play a role in substrate specificity.

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“…Synthetic medium contained 2% glucose, 0.7% yeast nitrogen base without amino acids (Difco), 50 mM MES [2. (N-morpholino) ethanosulfonic acid] adjusted to pH 6.0 with Tris and the amino acids, purine and pyrimidine bases required by the strains.Strains YPH499 (MATs ura3 leu2 his3 trpl lys2 ado2) and JBY10 (isogonic to YPH499 with hogl.Al:: TRPI) [6] were obtained from Dr. M. Gustin (Houston). The hogl hal3 double mutant was obtained by generation of a hal3::LEU2 gonomic deletion in the JBYI0 background as described [10].…”

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confidence: 99%

Multiple transduction pathways regulate the sodium‐extrusion gene PMR2/ENA1 during salt stress in yeast

1996

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The yeast PMR21£NAI gene encodes an ATPase involved in sodium extrusion and induced by NaCI. At low salt concentrations (0.3 1VID induction is mediated by the HOG-MAP kinase pathway, a system activated by non-specific osmotic stre&~. At high salt concentrations (0.8 M) induction i~ mediated by the protein phosphatase caleineurin and is specific for sodium. Protein kinase A and Sis2ptHal3p modulate PMR21£NAI expression as negative and positive factors, respectively but Sis2p/Hal3p does not perticipate in the transduction of the salt signal. Salt stress dect'eases the level of cAMP and the resulting decrease in protein kinase A activity may contribute t6 HOGmediated Induction.Key words: Signal transduction; Salt stress; MAP kinase; Calcineurin; cAMP; Saccharomyces cerevisiae 1. Introductit, n Living cells can withstand a variety of stress conditions such as extreme temperatures, water deficit, high salt concentrations, starvation etc. Under these circumstances organisms modify their cellular machinery in order to counteract the deleterious effect of damaging agents. This constitutes a stress response and involves modulation of enzymatic activities as well as changes in gene expression [1,2]. In ~'ecent years considerable interest has been raised by the mechanisms of plant tolerance to drought and salinity, two major factors limiting agricultural productivity [3]. The signal transduction pathways operating during osmotic and salt stress are only partially understood and this gap of knowledge is a limiting factor for urgent biotechnological applications [2].The yeast Saccharomyces cerevisiae can be utilized as a convenient model system in salinity studies [2]. Salt stress has two major harmful effects for cells: the loss of turgor pressure and the toxicity of Na ÷ ions to cellular metabolism. The adaptation of yeast to these conditions requires the modification of the plasma membrane transport systems to exclude Na + ions from the cytosol and the onset of glycerol synthesis to restore turgor pressure. This adaptation is largely based on changes in the expression of key genes such as PMR21ENAI (in the following referred to as ENAI), encoding an ATPase involved in sodium extrusion [4], and GPDI, encoding~a dehydrogenase involved in gljcerol synthesis [5]. Many other genes are also induced by saP, stress whose contribution to the adaptatio,a, if any, is not well understood [2].In the present work we have investigated the environmental signals and tran,,~lucing pathways mediating the induction of *Corresponding author'. Fax: (34) (6) Materials and methodsYPD and synthetic medium were prepared as described [12]. YPD contained 2% glucose, 1% yeast extract and 2% peptone. Synthetic medium contained 2% glucose, 0.7% yeast nitrogen base without amino acids (Difco), 50 mM MES [2.(N-morpholino) ethanosulfonic acid] adjusted to pH 6.0 with Tris and the amino acids, purine and pyrimidine bases required by the strains.Strains YPH499 (MATs ura3 leu2 his3 trpl lys2 ado2) and JBY10 (isogonic to YPH499 with hogl.Al:: TRPI) ...

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An Osmosensing Signal Transduction Pathway in Yeast

Cited by 1,179 publications

References 33 publications

Integrated cellular network of transcription regulations and protein-protein interactions

Integrated cellular network of transcription regulations and protein-protein interactions

**Characterization of SKM1, a Saccharomyces cerevisiae gene encoding a novel Ste20/PAK‐like protein kinase**

Multiple transduction pathways regulate the sodium‐extrusion gene PMR2/ENA1 during salt stress in yeast

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