Type 2C protein phosphatase Ptc6 participates in activation of the Slt2-mediated cell wall integrity pathway in Saccharomyces cerevisiae

Sharmin, Dilruba; Sasano, Yu; Sugiyama, Minetaka; Harashima, Satoshi

doi:10.1016/j.jbiosc.2014.09.013

Cited by 6 publications

(6 citation statements)

References 39 publications

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“…We also verified whether VPA promotes Slt2 dephosphorylation. Contrary to this notion, neither genes encoding Slt2 phosphatases353738 ( SDP1, MSG5, PTP2, PTP3 ), nor ones that dephosphorylate its activating kinases Mkk1/23940 ( PTC1, PTC6 ), were upregulated by VPA (Supplementary Table S1). Consistently, VPA-induced abrogation of Slt2 phosphorylation was observed in cells devoid of the aforementioned phosphatases (Supplementary Fig.…”

Section: Resultsmentioning

confidence: 83%

Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae

Desfossés-Baron

Hammond-Martel

Simoneau

et al. 2016

Sci Rep

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The mechanism of action of valproate (VPA), a widely prescribed short chain fatty acid with anticonvulsant and anticancer properties, remains poorly understood. Here, the yeast Saccharomyces cerevisiae was used as model to investigate the biological consequences of VPA exposure. We found that low pH strongly potentiates VPA-induced growth inhibition. Transcriptional profiling revealed that under these conditions, VPA modulates the expression of genes involved in diverse cellular processes including protein folding, cell wall organisation, sexual reproduction, and cell cycle progression. We further investigated the impact of VPA on selected processes and found that this drug: i) activates markers of the unfolded protein stress response such as Hac1 mRNA splicing; ii) modulates the cell wall integrity pathway by inhibiting the activation of the Slt2 MAP kinase, and synergizes with cell wall stressors such as micafungin and calcofluor white in preventing yeast growth; iii) prevents activation of the Kss1 and Fus3 MAP kinases of the mating pheromone pathway, which in turn abolishes cellular responses to alpha factor; and iv) blocks cell cycle progression and DNA replication. Overall, our data identify heretofore unknown biological responses to VPA in budding yeast, and highlight the broad spectrum of cellular pathways influenced by this chemical in eukaryotes.

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Section: Resultsmentioning

confidence: 83%

Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae

Desfossés-Baron

Hammond-Martel

Simoneau

et al. 2016

Sci Rep

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“…Signal Transduction.-The phosphatases of the PPM family are involved in a number of cellular functions. These phosphatases are functionally redundant, particularly in regard to cold response, high temperature stress, as well as with Li 2+ , Na 2+ , and caffeine sensitivity (Sharmin et al, 2015). Ptc1 is required for the transition between the G2 phase and M phase of the cell cycle by activating the cell wall integrity (CWI) pathway through dephosphorylation of Mkk1, a MAPK kinase (Tatjer et al, 2016).…”

Section: Ppm Familymentioning

confidence: 99%

“…Ptc1 is required for cortical ER inheritance to help facilitate ER tubule spreading across the bud cortex (Li et al, 2013). Ptc6 is involved in the CWI pathway by negatively regulating the MAP kinase, Slt2 (Sharmin et al, 2015). Ptc7 dephosphorylates the hydrolase Coq7 (Cat5) activating coenzyme Q6 biosynthesis (Martin-Montalvo et al, 2013).…”

Section: Ppm Familymentioning

confidence: 99%

Protein phosphatases of Saccharomyces cerevisiae

Offley

Schmidt

2018

Curr Genet

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The phosphorylation status of a protein is highly regulated and is determined by the opposing activities of protein kinases and protein phosphatases within the cell. While much is known about the protein kinases found in Saccharomyces cerevisiae, the protein phosphatases are much less characterized. Of the 127 protein kinases in yeast, over 90% are in the same evolutionary lineage. In contrast, protein phosphatases are fewer in number (only 43 have been identified in yeast) and comprise multiple, distinct evolutionary lineages. Here we review the protein phosphatase families of yeast with regard to structure, catalytic mechanism, regulation, and signal transduction participation.

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“…The inactivation of both PTC1 and the MAPK SLT2 in yeast provoked cells extremely sensitive to cell wall damage agents (Gonzalez et al , ). Additionally, PTC6 was reported to participate in the activation of the SLT2‐mediated cell wall integrity (Sharmin et al , ).…”

Section: Discussionmentioning

confidence: 99%

“…PTC5 and PTC6, but not PTC7, in concert with protein kinases PKP1 and PKP2, regulate the reversible phosphorylation of PDA1, the E1 alpha subunit of the PDH complex in S. cerevisiae (Gey et al , ; Krause‐Buchholz et al , ; Tal et al , ). Additionally, PTC6 regulates positively SLT2 signalling in S. cerevisiae (Sharmin et al , ) and is required for mitochondrial autophagy as well as for rapamycin and caffeine sensitivity (Gey et al , ; Ruan et al , ; Sakumoto et al , ). CaPTC6 and CaPTC7 are phosphatases involved in C. albicans tolerance to azoles (Zhao et al , ).…”

Section: Introductionmentioning

confidence: 99%

The phosphatase Ptc6 is involved in virulence and MAPK signalling in Fusarium oxysporum

Nunez-Rodriguez

Ruiz‐Roldán

Lemos

et al. 2019

Molecular Plant Pathology

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Mitogen-activated kinase (MAPK) signalling pathways are involved in several important processes related to the development and virulence of Fusarium oxysporum. Reversible phosphorylation of the protein members of these pathways is a major regulator of essential biological processes. Among the phosphatases involved in dephosphorylation of MAPKs, type 2C protein phosphatases (PP2Cs) play important roles regulating many developmental strategies and stress responses in yeasts. Nevertheless, the PP2C family is poorly known in filamentous fungi. The F. oxysporum PP2C family includes seven proteins, but only Ptc1 has been studied so far. Here we show the involvement of Ptc6 in the stress response and virulence of F. oxysporum. Expression analysis revealed increased expression of ptc6 in response to cell wall and oxidative stresses. Additionally, targeted inactivation of ptc6 entailed enhanced susceptibility to cell wall stresses caused by Calcofluor White (CFW). We also demonstrate that the lack of Ptc6 deregulates both the Mpk1 phosphorylation induced by CFW and, more importantly, the Fmk1 dephosphorylation induced by pH acidification of the extracellular medium, indicating that Ptc6 is involved in the regulation of these MAPKs. Finally, we showed, for the first time, the involvement of a phosphatase in the invasive growth and virulence of F. oxysporum.

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Type 2C protein phosphatase Ptc6 participates in activation of the Slt2-mediated cell wall integrity pathway in Saccharomyces cerevisiae

Cited by 6 publications

References 39 publications

Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae

Valproate inhibits MAP kinase signalling and cell cycle progression in S. cerevisiae

Protein phosphatases of Saccharomyces cerevisiae

The phosphatase Ptc6 is involved in virulence and MAPK signalling in Fusarium oxysporum

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