Different roles for the stress-activated protein kinase pathway in the regulation of trehalose metabolism in Schizosaccharomyces pombe

Microbiology ◽  
2003 ◽  
Vol 149 (7) ◽  
pp. 1745-1752 ◽  
Author(s):  
V. Paredes ◽  
A. Franco ◽  
T. Soto ◽  
J. Vicente-Soler ◽  
M. Gacto ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Transcription Factors ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Stress Responses ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Trehalose Metabolism

The Wis1p-Sty1p mitogen-activated protein kinase cascade is a major signalling system in the fission yeast Schizosaccharomyces pombe for a wide range of stress responses. It is known that trehalose functions as a protective metabolite to counteract deleterious effects of environmental stresses. Herein it is reported that the expression of genes related to trehalose metabolism in S. pombe, ntp1 + (neutral trehalase) and tps1 + [trehalose-6-phosphate (T6P) synthase], is partially regulated by the Sty1p kinase under salt-induced osmotic stress and conditions of slight oxidative stress and is fully dependent on this kinase under severe oxidative stress. This control is carried out through transcription factors Atf1p/Pcr1p during osmotic stress and through Pap1p during exposure to low levels of oxidative stress. However, all three transcription factors are needed for gene expression under conditions of extreme oxidative stress. In addition, a role for Sty1p in the modulation of post-transcriptional activation of trehalase mediated by Pka1p/Sck1p kinases, as well as in the activity of T6P synthase under such stressful conditions has been demonstrated. These results reveal a novel dual action of the Wis1p-Sty1p pathway in the regulation of trehalose metabolism in fission yeast.

scholarly journals Distinct Regulatory Proteins Control the Graded Transcriptional Response to Increasing H2O2 Levels in Fission Yeast Schizosaccharomyces pombe

2002 ◽  
Vol 13 (3) ◽  
pp. 805-816 ◽  
Author(s):  
Janet Quinn ◽  
Victoria J. Findlay ◽  
Keren Dawson ◽  
Jonathan B.A. Millar ◽  
Nic Jones ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Transcriptional Response ◽  
Regulatory Proteins ◽  
Mitogen Activated Protein Kinase ◽  
Two Component ◽  
Mitogen Activated Protein ◽  
Low Levels

The signaling pathways that sense adverse stimuli and communicate with the nucleus to initiate appropriate changes in gene expression are central to the cellular stress response. Herein, we have characterized the role of the Sty1 (Spc1) stress-activated mitogen-activated protein kinase pathway, and the Pap1 and Atf1 transcription factors, in regulating the response to H2O2 in the fission yeast Schizosaccharomyces pombe. We find that H2O2 activates the Sty1 pathway in a dose-dependent manner via at least two sensing mechanisms. At relatively low levels of H2O2, a two component-signaling pathway, which feeds into either of the two stress-activated mitogen-activated protein kinase kinase kinases Wak1 or Win1, regulates Sty1 phosphorylation. In contrast, at high levels of H2O2, Sty1 activation is controlled predominantly by a two-component independent mechanism and requires the function of both Wak1 and Win1. Individual transcription factors were also found to function within a limited range of H2O2 concentrations. Pap1 activates target genes primarily in response to low levels of H2O2, whereas Atf1 primarily controls the transcriptional response to high concentrations of H2O2. Our results demonstrate that S. pombe uses a combination of stress-responsive regulatory proteins to gauge and effect the appropriate transcriptional response to increasing concentrations of H2O2.

scholarly journals Stress-Activated Protein Kinase Pathway Functions To Support Protein Synthesis and Translational Adaptation in Response to Environmental Stress in Fission Yeast

2005 ◽  
Vol 4 (11) ◽  
pp. 1785-1793 ◽  
Author(s):  
Isabelle Dunand-Sauthier ◽  
Carol A. Walker ◽  
Jana Narasimhan ◽  
Amanda K. Pearce ◽  
Ronald C. Wek ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Environmental Stress ◽  
Fission Yeast ◽  
Translation Initiation ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Eif2α Phosphorylation ◽  
Mitogen Activated Protein

ABSTRACT The stress-activated protein kinase (SAPK) pathway plays a central role in coordinating gene expression in response to diverse environmental stress stimuli. We examined the role of this pathway in the translational response to stress in Schizosaccharomyces pombe. Exposing wild-type cells to osmotic stress (KCl) resulted in a rapid but transient reduction in protein synthesis. Protein synthesis was further reduced in mutants disrupting the SAPK pathway, including the mitogen-activated protein kinase Wis1 or the mitogen-activated protein kinase Spc1/Sty1, suggesting a role for these stress response factors in this translational control. Further polysome analyses revealed a role for Spc1 in supporting translation initiation during osmotic stress, and additionally in facilitating translational adaptation. Exposure to oxidative stress (H2O2) resulted in a striking reduction in translation initiation in wild-type cells, which was further reduced in spc1 − cells. Reduced translation initiation correlated with phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) in wild-type cells. Disruption of Wis1 or Spc1 kinase or the downstream bZip transcription factors Atf1 and Pap1 resulted in a marked increase in eIF2α phosphorylation which was dependent on the eIF2α kinases Hri2 and Gcn2. These findings suggest a role for the SAPK pathway in supporting translation initiation and facilitating adaptation to environmental stress in part through reducing eIF2α phosphorylation in fission yeast.

scholarly journals The Mitogen-Activated Protein Kinase BcSak1 of Botrytis cinerea Is Required for Pathogenic Development and Has Broad Regulatory Functions Beyond Stress Response

2012 ◽  
Vol 25 (6) ◽  
pp. 802-816 ◽  
Author(s):  
Jens Heller ◽  
Nadja Ruhnke ◽  
José Juan Espino ◽  
Michelli Massaroli ◽  
Isidro Gonzalez Collado ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stress Response ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Botrytis Cinerea ◽  
Fluorescent Protein ◽  
Mitogen Activated Protein Kinase ◽  
In Planta ◽  
Mitogen Activated Protein

The mitogen-activated protein kinase (MAPK) BcSak1 of Botrytis cinerea is activated upon exposure to H2O2 and, hence, might be involved in coping with oxidative stress during infection. However, beside osmotic and oxidative stress sensitivity, Δbcsak1 mutants have a pleiotropic phenotype, as they do not produce conidia and are unable to penetrate unwounded host tissue. In this study, the role of BcSak1 was investigated in the stress response and during infection of French beans by Botrytis cinerea. Using a macroarray approach, it was shown that BcSak1 is only marginally involved in the specific oxidative stress response. In fact, the induction of several genes after oxidative stress treatment is BcSak1-dependent, but most of these genes are also induced under conditions of osmotic stress. The majority of genes regulated by BcSak1 are not involved in the stress response at all. Using a translational fusion of BcSak1 to green fluorescent protein, it was shown clearly that the localization of this MAPK depends on the type of stress being applied; it associates rapidly to the nucleus only under osmotic stress. Therefore, a model is proposed in which BcSak1 acts in the cytosol by activation of one or more transcription factors under oxidative stress and, at the same time, it reacts to osmotic stress by migrating to the nucleus. Interestingly, the MAPK is also involved in the regulation of secondary metabolism, as the major phytotoxins secreted by this fungus are reduced in the Δbcsak1 deletion mutant. Experiments done in planta underlined the essential role of BcSak1 in the early stages of infection, when it translocates to the nucleus and then changes to cytosolic distribution during hyphal growth within the tissue.

scholarly journals Histatin 5 Initiates Osmotic Stress Response in Candida albicans via Activation of the Hog1 Mitogen-Activated Protein Kinase Pathway

2007 ◽  
Vol 6 (10) ◽  
pp. 1876-1888 ◽  
Author(s):  
Slavena Vylkova ◽  
Woong Sik Jang ◽  
Wansheng Li ◽  
Namrata Nayyar ◽  
Mira Edgerton
Keyword(s):  
Oxidative Stress ◽  
Candida Albicans ◽  
Stress Response ◽  
Protein Kinase ◽  
Osmotic Stress ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Hog Pathway ◽  
Histatin 5 ◽  
Mitogen Activated Protein

ABSTRACT Histatin 5 (Hst 5) is a salivary cationic peptide that has toxicity for Candida albicans by inducing rapid cellular ion imbalance and cell volume loss. Microarray analyses of peptide-treated cells were used to evaluate global gene responses elicited by Hst 5. The major transcriptional response of C. albicans to Hst 5 was expression of genes involved in adaptation to osmotic stress, including production of glycerol (RHR2, SKO1, and PDC11) and the general stress response (CTA1 and HSP70). The oxidative-stress genes AHP1, TRX1, and GPX1 were mildly induced by Hst 5. Cell defense against Hst 5 was dependent on the Hog1 mitogen-activated protein kinase (MAPK) pathway, since C. albicans hog1/hog1 mutants were significantly hypersensitive to Hst 5 but not to Mkc1 MAPK or Cek1 MAPK mutants. Activation of the high-osmolarity glycerol (HOG) pathway was demonstrated by phosphorylation of Hog1 MAPK as well as by glycerol production following Hst 5 treatment in a dose-dependent manner. C. albicans cells prestressed with sorbitol were less sensitive to subsequent Hst 5 treatment; however, cells treated concurrently with osmotic stress and Hst 5 were hypersensitive to Hst 5. In contrast, cells subjected to oxidative stress had no difference in sensitivity to Hst 5. These results suggest a common underlying cellular response to osmotic stress and Hst 5. The HOG stress response pathway likely represents a significant and effective challenge to physiological levels of Hst 5 and other toxic peptides in fungal cells.

scholarly journals Fission Yeast Mitogen-Activated Protein Kinase Sty1 Interacts with Translation Factors

2007 ◽  
Vol 7 (2) ◽  
pp. 328-338 ◽  
Author(s):  
Eva Asp ◽  
Daniel Nilsson ◽  
Per Sunnerhagen
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Fission Yeast ◽  
Elongation Factor ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Translation Efficiency ◽  
Nitrogen Deprivation ◽  
Hyperosmotic Shock ◽  
Mitogen Activated Protein

ABSTRACT Signaling by stress-activated mitogen-activated protein kinase (MAPK) pathways influences translation efficiency in mammalian cells and budding yeast. We have investigated the stress-activated MAPK from fission yeast, Sty1, and its downstream protein kinase, Mkp1/Srk1, for physically associated proteins using tandem affinity purification tagging. We find Sty1, but not Mkp1, to bind to the translation elongation factor eukaryotic elongation factor 2 (eEF2) and the translation initiation factor eukaryotic initiation factor 3a (eIF3a). The Sty1-eIF3a interaction is weakened under oxidative or hyperosmotic stress, whereas the Sty1-eEF2 interaction is stable. Nitrogen deprivation causes a transient strengthening of both the Sty1-eEF2 and the Sty1-Mkp1 interactions, overlapping with the time of maximal Sty1 activation. Analysis of polysome profiles from cells under oxidative stress, or after hyperosmotic shock or nitrogen deprivation, shows that translation in sty1 mutant cells recovers considerably less efficiently than that in the wild type. Cells lacking the Sty1-regulated transcription factor Atf1 are deficient in maintaining and recovering translational activity after hyperosmotic shock but not during oxidative stress or nitrogen starvation. In cells lacking Sty1, eIF3a levels are decreased, and phosphorylation of eIF3a is reduced. Taken together, our data point to a central role in translational adaptation for the stress-activated MAPK pathway in fission yeast similar to that in other investigated eukaryotes, with the exception that fission yeast MAPK-activated protein kinases seem not to be directly involved in this process.

scholarly journals Role of Mitogen-Activated Protein Kinase Sty1 in Regulation of Eukaryotic Initiation Factor 2α Kinases in Response to Environmental Stress in Schizosaccharomyces pombe

2009 ◽  
Vol 9 (1) ◽  
pp. 194-207 ◽  
Author(s):  
Juan José Berlanga ◽  
Damariz Rivero ◽  
Ruth Martín ◽  
Saturnino Herrero ◽  
Sergio Moreno ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heat Shock ◽  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Mitogen Activated Protein Kinase ◽  
Initiation Factor ◽  
Eukaryotic Initiation Factor ◽  
Transcriptional Responses ◽  
Mitogen Activated Protein ◽  
Eif2α Kinase

ABSTRACT The mitogen-activated protein kinase (MAPK) Sty1 is essential for the regulation of transcriptional responses that promote cell survival in response to different types of environmental stimuli in Schizosaccharomyces pombe. In fission yeast, three distinct eukaryotic initiation factor 2α (eIF2α) kinases, two mammalian HRI-related protein kinases (Hri1 and Hri2) and the Gcn2 ortholog, regulate protein synthesis in response to cellular stress conditions. In this study, we demonstrate that both Hri1 and Hri2 exhibited an autokinase activity, specifically phosphorylated eIF2α, and functionally replaced the endogenous Saccharomyces cerevisiae Gcn2. We further show that Gcn2, but not Hri1 or Hri2, is activated early after exposure to hydrogen peroxide and methyl methanesulfonate (MMS). Cells lacking Gcn2 exhibit a later activation of Hri2. The activated MAPK Sty1 negatively regulates Gcn2 and Hri2 activities under oxidative stress but not in response to MMS. In contrast, Hri2 is the primary activated eIF2α kinase in response to heat shock. In this case, the activation of Sty1 appears to be transitory and does not contribute to the modulation of the eIF2α kinase stress pathway. In strains lacking Hri2, a type 2A protein phosphatase is activated soon after heat shock to reduce eIF2α phosphorylation. Finally, the MAPK Sty1, but not the eIF2α kinases, is essential for survival upon oxidative stress or heat shock, but not upon MMS treatment. These findings point to a regulatory coordination between the Sty1 MAPK and eIF2α kinase pathways for a particular range of stress responses.

scholarly journals Activation and regulation of the Spc1 stress-activated protein kinase in Schizosaccharomyces pombe.

1996 ◽  
Vol 16 (6) ◽  
pp. 2870-2877 ◽  
Author(s):  
G Degols ◽  
K Shiozaki ◽  
P Russell
Keyword(s):  
Protein Kinase ◽  
Osmotic Stress ◽  
Schizosaccharomyces Pombe ◽  
Tyrosine Phosphatase ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Expression Of Genes ◽  
In The Wild

Spc1, an osmotic-stress-stimulated mitogen-activated protein kinase (MAPK) homolog in the fission yeast Schizosaccharomyces pombe, is required for the induction of mitosis and survival in high-osmolarity conditions. Spc1, also known as Sty1, is activated by Wis1 MAPK kinase and inhibited by Pyp1 tyrosine phosphatase. Spc1 is most closely related to Saccharomyces cerevisiae Hog1 and mammalian p38 kinases. Whereas Hog1 is specifically responsive to osmotic stress, we report here that Spc1 is activated by multiple forms of stress, including high temperature and oxidative stress. In this regard Spc1 is more similar to mammalian p38. Activation of Spc1 is crucial for survival of various forms of stress. Spc1 regulates expression of genes encoding stress-related proteins such as glycerol-3-phosphate dehydrogenase (gpd1+) and trehalose-6-phosphate synthase (tps1+). Spc1 also promotes expression of pyp2+, which encodes a tyrosine phosphatase postulated as a negative regulator of Spc1. This proposal is supported by the finding that Spc1 associates with Pyp2 in vivo and that the amount of Spc1 tyrosine phosphorylation is lower in a Pyp2-overproducing strain than in the wild type. Moreover, the level of stress-stimulated gpd1+ expression is higher in delta pyp2 mutants than in the wild type. These findings demonstrate that Spc1 promotes expression of genes involved in stress survival and that of regulation may be commonly employed to modulate MAPK signal transduction pathways in eukaryotic species.

scholarly journals Transduction of centrifugation-induced gravity forces through mitogen-activated protein kinase pathways in the fission yeast Schizosaccharomyces pombe

Microbiology ◽  
2007 ◽  
Vol 153 (5) ◽  
pp. 1519-1529 ◽  
Author(s):  
Teresa. Soto ◽  
Andrés. Núñez ◽  
Marisa. Madrid ◽  
Jero. Vicente ◽  
Mariano. Gacto ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
Fission Yeast ◽  
Mitogen Activated Protein Kinase ◽  
Induced Gravity ◽  
Gravity Forces ◽  
Mitogen Activated Protein

scholarly journals DictyosteliumStress-activated Protein Kinase α, a Novel Stress-activated Mitogen-activated Protein Kinase Kinase Kinase-like Kinase, Is Important for the Proper Regulation of the Cytoskeleton

2003 ◽  
Vol 14 (11) ◽  
pp. 4526-4540 ◽  
Author(s):  
Binggang Sun ◽  
Hui Ma ◽  
Richard A. Firtel
Keyword(s):  
Protein Kinase ◽  
Osmotic Stress ◽  
Stress Responses ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Functions ◽  
Developmental Defects ◽  
Cellular Processes ◽  
Mitogen Activated Protein ◽  
Cgmp Analog ◽  
Protein Kinase Kinase

Mitogen-activated protein kinase cascades regulate various cellular functions, including growth, cell differentiation, development, and stress responses. We have identified a new Dictyostelium kinase (stress-activated protein kinase [SAPK]α), which is related to members of the mixed lineage kinase class of mitogen-activated protein kinase kinases. SAPKα is activated by osmotic stress, heat shock, and detachment from the substratum and by a membrane-permeable cGMP analog, a known regulator of stress responses in Dictyostelium. SAPKα is important for cellular resistance to stresses, because SAPKα null cells exhibit reduced viability in response to osmotic stress. We found that SAPKα mutants affect cellular processes requiring proper regulation of the actin cytoskeleton, including cell motility, morphogenesis, cytokinesis, and cell adhesion. Overexpression of SAPKα results in highly elevated basal and chemoattractant-stimulated F-actin levels and strong aggregation and developmental defects, including a failure to polarize and chemotax, and abnormal morphogenesis. These phenotypes require a kinase-active SAPKα. SAPKα null cells exhibit reduced chemoattractant-stimulated F-actin levels, cytokinesis, developmental and adhesion defects, and a motility defect that is less severe than that exhibited by SAPKα-overexpressing cells. SAPKα colocalizes with F-actin in F-actin–enriched structures, including membrane ruffles and pseudopodia during chemotaxis. Although SAPKα is required for these F-actin–mediated processes, it is not detectably activated in response to chemoattractant stimulation.

Age-Related Changes in Activation of Mitogen-Activated Protein Kinase Cascades by Oxidative Stress

1998 ◽  
Vol 3 (1) ◽  
pp. 23-27 ◽  
Author(s):  
Kathryn Z Guyton ◽  
Myriani Gorospe ◽  
Xiantao Wang ◽  
Yolanda D Mock ◽  
Gertrude C Kokkonen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Protein Kinase ◽  
Mitogen Activated Protein Kinase ◽  
Age Related ◽  
Mitogen Activated Protein ◽  
Age Related Changes
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