Regulation of the Saccharomyces cerevisiae Slt2 Kinase Pathway by the Stress-inducible Sdp1 Dual Specificity Phosphatase

Hahn, Jinyong; Thiele, Dennis J.

doi:10.1074/jbc.m202557200

Cited by 112 publications

(134 citation statements)

References 41 publications

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“…This result is similar to that previously obtained when the same mutant protein was assayed for its activity on the MAPK Fus3 (14). All of these findings indicate that phosphatase activity of Msg5 is responsible for the ob- (14,16,35). Therefore, we analyzed whether Msg5 might be somehow regulated by posttranscriptional modifications.…”

Section: Two-hybrid Analysis Of the Msg5 And Slt2supporting

confidence: 68%

“…Besides, the involvement of Msg5 in the maintenance of a low basal level of activity through the cell integrity pathway has been suggested because the disruption of MSG5 results in increased phosphoSlt2 levels under non-inducing conditions (15). The second one, Sdp1, has recently been shown to target Slt2, regulating the phosphorylation level of this MAPK in response to heat shock (16,17).…”

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confidence: 99%

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Reciprocal Regulation between Slt2 MAPK and Isoforms of Msg5 Dual-specificity Protein Phosphatase Modulates the Yeast Cell Integrity Pathway

Flández

Cosano

Nombela

et al. 2004

Journal of Biological Chemistry

101

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Dual-specificity protein phosphatases (DSPs) are involved in the negative regulation of mitogen-activated protein kinases (MAPKs) by dephosphorylating both threonine-and tyrosine-conserved residues located at the activation loop. Here we show that Msg5 DSP activity is essential for maintaining a low level of signaling through the cell integrity pathway in Saccharomyces cerevisiae. Consistent with a role of this phosphatase on cell wall physiology, cells lacking Msg5 displayed an increased sensitivity to the cell wall-interfering compound Congo Red. We have observed that the N-terminal non-catalytic region of this phosphatase was responsible for binding to the kinase domain of Slt2, the MAPK that operates in this pathway. In vivo and in vitro experiments revealed that both proteins act on each other. Msg5 bound and dephosphorylated activated Slt2. Reciprocally, Slt2 phosphorylated Msg5 as a consequence of the activation of the cell integrity pathway. In addition, alternative use of translation initiation sites at MSG5 resulted in two protein forms that are functional on Slt2 and became equally phosphorylated following activation of this MAPK. Under activating conditions, a decrease in the affinity between Msg5 and Slt2 was observed, leading us to suggest that the mechanism by which Slt2 controls the action of Msg5 was via the modulation of protein-protein interactions. Our results indicate the existence of posttranscriptional mechanisms of regulation of DSPs in yeast and provide new insights into the negative control of the cell integrity pathway.

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Section: Two-hybrid Analysis Of the Msg5 And Slt2supporting

confidence: 68%

mentioning

confidence: 99%

Reciprocal Regulation between Slt2 MAPK and Isoforms of Msg5 Dual-specificity Protein Phosphatase Modulates the Yeast Cell Integrity Pathway

Flández

Cosano

Nombela

et al. 2004

Journal of Biological Chemistry

101

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“…The significant reduction of RLM1 transcription in hog1⌬ mutants implicates the involvement of Hog1 in RLM1 reporter activation by hydrogen peroxide. It has been suggested that Hog1 can regulate Rlm1 activity by unknown mechanisms under hyperosmotic stress conditions (Hahn and Thiele, 2002). On the other hand, we did not observe a difference in the phosphorylation of Mpk1 in hog1 mutant cells, suggesting that Hog1 regulation of Rlm1 and Mpk1 activation by hydrogen peroxide have different upstream regulators.…”

Section: Discussioncontrasting

confidence: 49%

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Staleva

Hall

Orlow

2004

MBoC

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Mating in haploid Saccharomyces cerevisiae occurs after activation of the pheromone response pathway. Biochemical components of this pathway are involved in other yeast signal transduction networks. To understand more about the coordination between signaling pathways, we used a "chemical genetic" approach, searching for compounds that would activate the pheromone-responsive gene FUS1 and RLM1, a reporter for the cell integrity pathway. We found that catecholamines (L-3,4-hydroxyphenylalanine [L-dopa], dopamine, adrenaline, and noradrenaline) elevate FUS1 and RLM1 transcription. N-Acetyl-cysteine, a powerful antioxidant in yeast, completely reversed this effect, suggesting that FUS1 and RLM1 activation in response to catecholamines is a result of oxidative stress. The oxidant hydrogen peroxide also was found to activate transcription of an RLM1 reporter. Further genetic analysis combined with immunoblotting revealed that Kss1, one of the mating mitogen-activated protein kinases (MAPKs), and Mpk1, an MAPK of the cell integrity pathway, participated in L-dopa-induced stimulation of FUS1 and RLM1 transcription. We also report that Mpk1 and Hog1, the high osmolarity MAPK, were phosphorylated upon induction by hydrogen peroxide. Together, our results demonstrate that cells respond to oxidative stress via different signal transduction machinery dependent upon the nature of the oxidant. INTRODUCTIONIn the haploid cells of the yeast Saccharomyces cerevisiae, four essential MAPK cascades (Figure 1) respond to different external signals to mediate specific responses. The mating pathway is activated by peptide pheromones and induces cell-cycle arrest and the morphological changes required for mating (Elion, 1998;Gustin et al., 1998). The invasive growth pathway is activated by starvation and induces foraging into the agar substratum. The high osmolarity glycerol (HOG) pathway increases intracellular glycerol levels in response to hypertonic stress, whereas the cell integrity pathway is activated by hypotonic stress, heat shock, or impaired cell wall synthesis. Recently, an additional MAPK cascade has been described: the Kss1 vegetative growth pathway (Lee and Elion, 1999). The Kss1 pathway may be activated by cell wall stress or changes in osmolarity (Cullen et al., 2000).The mating pathway is the most studied cellular response to an external signal. As a relatively simple G protein-coupled cascade, it is a widely used model to study mammalian G protein-coupled receptors. The mating cascade includes pheromone receptors (Ste2 and Ste3), G proteins (Gpa1, Ste4, and Ste18), the p21 activating protein kinase Ste20, a mitogen-activated protein kinase kinase kinase (MAPKKK) Ste11, a mitogen-activated protein kinase kinase (MAPKK) Ste7, a scaffolding protein Ste5 and two MAPKs (Fus3 and Kss1) (Gustin et al., 1998;Madhani and Fink, 1998;Farley et al., 1999). Targets of the terminal MAPK include Ste12, a factor required for transcription of pheromone-responsive genes, and Far1, a bifunctional protein required for polarization and G1...

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“…Ptp2 and 3, as well as the type 2C protein phosphatase (PP2C) Ptc1 antagonize the osmosensing MAPK cascade by dephosphorylating Hog1 (Warmka et al, 2001;Wurgler-Murphy et al, 1997). The stress-inducible dualspecificity MAPK phosphatase Sdp1 negatively regulates the cell integrity pathway by dephosphorylating Mpk1 (Hahn and Thiele, 2002). In general, orthologues of these protein phosphatases were detected in all fungal species surveyed, suggesting that the mechanisms of regulating MAPK activity via dephosphorylation are broadly conserved in fungi.…”

Section: Mapk-regulatory Protein Phosphatasesmentioning

confidence: 99%

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

Rispail

Soanes

Ant

et al. 2009

Fungal Genetics and Biology

285

281

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a b s t r a c tMitogen-activated protein kinase (MAPK) cascades and the calcium-calcineurin pathway control fundamental aspects of fungal growth, development and reproduction. Core elements of these signalling pathways are required for virulence in a wide array of fungal pathogens of plants and mammals. In this review, we have used the available genome databases to explore the structural conservation of three MAPK cascades and the calcium-calcineurin pathway in ten different fungal species, including model organisms, plant pathogens and human pathogens. While most known pathway components from the model yeast Saccharomyces cerevisiae appear to be widely conserved among taxonomically and biologically diverse fungi, some of them were found to be restricted to the Saccharomycotina. The presence of multiple paralogues in certain species such as the zygomycete Rhizopus oryzae and the incorporation of new functional domains that are lacking in S. cerevisiae signalling proteins, most likely reflect functional diversification or adaptation as filamentous fungi have evolved to occupy distinct ecological niches.

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Regulation of the Saccharomyces cerevisiae Slt2 Kinase Pathway by the Stress-inducible Sdp1 Dual Specificity Phosphatase

Cited by 112 publications

References 41 publications

Reciprocal Regulation between Slt2 MAPK and Isoforms of Msg5 Dual-specificity Protein Phosphatase Modulates the Yeast Cell Integrity Pathway

Reciprocal Regulation between Slt2 MAPK and Isoforms of Msg5 Dual-specificity Protein Phosphatase Modulates the Yeast Cell Integrity Pathway

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Comparative genomics of MAP kinase and calcium–calcineurin signalling components in plant and human pathogenic fungi

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