scholarly journals The MAPKKKs Ste11 and Bck1 jointly transduce the high oxidative stress signal through the cell wall integrity MAP kinase pathway

2015 ◽  
Vol 2 (9) ◽  
pp. 329-342 ◽  
Author(s):  
Chunyan Jin ◽  
Stephen Kim ◽  
Stephen Willis ◽  
Katrina Cooper
Keyword(s):  
Oxidative Stress ◽  
Cell Wall ◽  
Map Kinase ◽  
Cell Wall Integrity ◽  
Stress Signal ◽  
High Oxidative Stress ◽  
Map Kinase Pathway ◽  
Kinase Pathway

scholarly journals WSC-1 and HAM-7 Are MAK-1 MAP Kinase Pathway Sensors Required for Cell Wall Integrity and Hyphal Fusion in Neurospora crassa

PLoS ONE ◽  
2012 ◽  
Vol 7 (8) ◽  
pp. e42374 ◽  
Author(s):  
Abhiram Maddi ◽  
Anne Dettman ◽  
Ci Fu ◽  
Stephan Seiler ◽  
Stephen J. Free
Keyword(s):  
Cell Wall ◽  
Map Kinase ◽  
Neurospora Crassa ◽  
Cell Wall Integrity ◽  
Hyphal Fusion ◽  
Map Kinase Pathway ◽  
Kinase Pathway

Response to high osmotic conditions and elevated temperature in Saccharomyces cerevisiae is controlled by intracellular glycerol and involves coordinate activity of MAP kinase pathways

Microbiology ◽  
2003 ◽  
Vol 149 (5) ◽  
pp. 1193-1204 ◽  
Author(s):  
Iwona Wojda ◽  
Rebeca Alonso-Monge ◽  
Jan-Paul Bebelman ◽  
Willem H. Mager ◽  
Marco Siderius
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Cell Wall ◽  
Osmotic Stress ◽  
Map Kinase ◽  
Growth Temperature ◽  
Wild Type ◽  
Hog Pathway ◽  
Map Kinase Pathway ◽  
Kinase Pathway ◽  
Intracellular Glycerol

In the yeast Saccharomyces cerevisiae, response to an increase in external osmolarity is mediated by the HOG (high osmolarity glycerol) MAP kinase pathway. HOG pathway mutant strains display osmosensitive phenotypes. Recently evidence has been obtained that the osmosensitivity of HOG pathway mutants is reduced during growth at elevated temperature (37 °C). A notable exception is the ste11ssk2ssk22 mutant, which displays hypersensitivity to osmotic stress at 37 °C. This paper reports that overexpression of FPS1 or GPD1 (encoding the glycerol transport facilitator and glycerol-3-phosphate dehydrogenase, respectively, and both affecting intracellular glycerol levels) reduces the hypersensitivity to osmotic stress of ste11ssk2ssk22 at 37 °C. Although in this particular HOG pathway mutant a correlation between suppression of the phenotype and glycerol content could be demonstrated, the absolute level of intracellular glycerol per se does not determine whether a strain is osmosensitive or not. Rather, evidence was obtained that the glycerol level may have an indirect effect, viz. by influencing signalling through the PKC (protein kinase C) MAP kinase pathway, which plays an important role in maintenance of cellular integrity. In order to validate the data obtained with a HOG pathway mutant strain for wild-type yeast cells, MAP kinase signalling under different growth conditions was examined in wild-type strains. PKC pathway signalling, which is manifest at elevated growth temperature by phosphorylation of MAP kinase Mpk1p, is rapidly lost when cells are shifted to high external osmolarity conditions. Expression of bck1-20 or overexpression of WSC3 in wild-type cells resulted in restoration of PKC signalling. Both PKC and HOG signalling, cell wall phenotypes and high osmotic stress responses in wild-type cells were found to be influenced by the growth temperature. The data taken together indicate the intricate interdependence of growth temperature, intracellular glycerol, cell wall structure and MAP kinase signalling in the hyperosmotic stress response of yeast.

scholarly journals Oxidative Stress Posttranslationally Regulates the Expression of Ha-Ras and Ki-Ras in Cultured Astrocytes

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Samantha Messina ◽  
Luigi Frati ◽  
Antonio Porcellini
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Map Kinase ◽  
Protein Synthesis Inhibitor ◽  
Synthesis Inhibitor ◽  
Cultured Astrocytes ◽  
Map Kinase Pathway ◽  
Safe Mechanism ◽  
Fail Safe ◽  
Kinase Pathway

Addition of hydrogen peroxide to cultured astrocytes induced a rapid and transient increase in the expression of Ha-Ras and Ki-Ras. Pull-down experiments with the GTP-Ras-binding domain of Raf-1 showed that oxidative stress substantially increased the activation of Ha-Ras, whereas a putative farnesylated activated form of Ki-Ras was only slightly increased. The increase in both Ha-Ras and Ki-Ras was insensitive to the protein synthesis inhibitor, cycloheximide, and was occluded by the proteasomal inhibitor, MG-132. In addition, exposure to hydrogen peroxide reduced the levels of ubiquitinated Ras protein, indicating that oxidative stress leads to a reduced degradation of both isoforms through the ubiquitin/proteasome pathway. Indeed, the late reduction in Ha-Ras and Ki-Ras was due to a recovery of proteasomal degradation because it was sensitive to MG-132. The late reduction of Ha-Ras levels was abrogated by compound PD98059, which inhibits the MAP kinase pathway, whereas the late reduction of Ki-Ras was unaffected by PD98059. We conclude that oxidative stress differentially regulates the expression of Ha-Ras and Ki-Ras in cultured astrocytes, and that activation of the MAP kinase pathway by oxidative stress itself or by additional factors may act as a fail-safe mechanism limiting a sustained expression of the potentially detrimental Ha-Ras.

scholarly journals The Cell Wall Sensors Mtl1, Wsc1, and Mid2 Are Required for Stress-Induced Nuclear to Cytoplasmic Translocation of Cyclin C and Programmed Cell Death in Yeast

2013 ◽  
Vol 2013 ◽  
pp. 1-15 ◽  
Author(s):  
Chunyan Jin ◽  
Andrey V. Parshin ◽  
Ira Daly ◽  
Randy Strich ◽  
Katrina F. Cooper
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Cell Wall ◽  
Programmed Cell Death ◽  
Map Kinase ◽  
Genetic Interaction ◽  
Negative Regulator ◽  
Cell Wall Integrity ◽  
Surprising Result ◽  
Cyclin C

Mtl1 is a member of a cell wall sensor family that monitors cell wall integrity in budding yeast. In response to cell wall stress, Mtl1 activates the cell wall integrity (CWI) MAP kinase pathway which transmits this signal to the nucleus to effect changes in gene expression. One target of the CWI MAP kinase is cyclin C, a negative regulator of stress response genes. CWI activation results in cyclin C relocalization from the nucleus to the cytoplasm where it stimulates programmed cell death (PCD) before it is destroyed. This report demonstrates that under low oxidative stress conditions, a combination of membrane sensors, Mtl1 and either Wsc1 or Mid2, are required jointly to transmit the oxidative stress signal to initiate cyclin C destruction. However, when exposed to elevated oxidative stress, additional pathways independent of these three sensor proteins are activated to destroy cyclin C. In addition,N-glycosylation is important for Mtl1 function as mutating the receptor residue (Asn42) or an enzyme required for synthesis ofN-acetylglucosamine (Gfa1) reduces sensor activity. Finally, combininggfa1-1with the cyclin C null allele induces a severe synthetic growth defect. This surprising result reveals a previously unknown genetic interaction between cyclin C and plasma membrane integrity.

scholarly journals Lrg1 Regulates β (1,3)-Glucan Masking in Candida albicans through the Cek1 MAP Kinase Pathway

mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Tian Chen ◽  
Andrew S. Wagner ◽  
Robert N. Tams ◽  
James E. Eyer ◽  
Sarah J. Kauffman ◽  
...  
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Map Kinase ◽  
Fungal Virulence ◽  
Content Type ◽  
Map Kinase Cascade ◽  
Kinase Cascade ◽  
Map Kinase Pathway ◽  
Immune Detection ◽  
Kinase Pathway

ABSTRACT Candida albicans is among the most prevalent opportunistic human fungal pathogens. The ability to mask the immunogenic polysaccharide β (1,3)-glucan from immune detection via a layer of mannosylated proteins is a key virulence factor of C. albicans. We previously reported that hyperactivation of the Cek1 mitogen-activated protein (MAP) kinase pathway promotes β (1,3)-glucan exposure. In this communication, we report a novel upstream regulator of Cek1 activation and characterize the impact of Cek1 activity on fungal virulence. Lrg1 encodes a GTPase-activating protein (GAP) that has been suggested to inhibit the GTPase Rho1. We found that disruption of LRG1 causes Cek1 hyperactivation and β (1,3)-glucan unmasking. However, when GTPase activation was measured for a panel of GTPases, the lrg1ΔΔ mutant exhibited increased activation of Cdc42 and Ras1 but not Rho1 or Rac1. Unmasking and Cek1 activation in the lrg1ΔΔ mutant can be blocked by inhibition of the Ste11 MAP kinase kinase kinase (MAPKKK), indicating that the lrg1ΔΔ mutant acts through the canonical Cek1 MAP kinase cascade. In order to determine how Cek1 hyperactivation specifically impacts virulence, a doxycycline-repressible hyperactive STE11ΔN467 allele was expressed in C. albicans. In the absence of doxycycline, this allele overexpressed STE11ΔN467, which induced production of proinflammatory tumor necrosis factor alpha (TNF-α) from murine macrophages. This in vitro phenotype correlates with decreased colonization and virulence in a mouse model of systemic infection. The mechanism by which Ste11ΔN467 causes unmasking was explored with RNA sequencing (RNA-Seq) analysis. Overexpression of Ste11ΔN467 caused upregulation of the Cph1 transcription factor and of a group of cell wall-modifying proteins which are predicted to impact cell wall architecture. IMPORTANCE Candida albicans is an important source of systemic infections in humans. The ability to mask the immunogenic cell wall polymer β (1,3)-glucan from host immune surveillance contributes to fungal virulence. We previously reported that the hyperactivation of the Cek1 MAP kinase cascade promotes cell wall unmasking, thus increasing strain immunogenicity. In this study, we identified a novel regulator of the Cek1 pathway called Lrg1. Lrg1 is a predicted GTPase-activating protein (GAP) that represses Cek1 activity by downregulating the GTPase Cdc42 and its downstream MAPKKK, Ste11. Upregulation of Cek1 activity diminished fungal virulence in the mouse model of infection, and this correlates with increased cytokine responses from macrophages. We also analyzed the transcriptional profile determined during β (1,3)-glucan exposure driven by Cek1 hyperactivation. Our report provides a model where Cek1 hyperactivation causes β (1,3)-glucan exposure by upregulation of cell wall proteins and leads to more robust immune detection in vivo, promoting more effective clearance.

scholarly journals Yeast Protein Kinases and the RHO1 Exchange Factor TUS1 Are Novel Components of the Cell Integrity Pathway in Yeast

2002 ◽  
Vol 22 (5) ◽  
pp. 1329-1339 ◽  
Author(s):  
Tobias Schmelzle ◽  
Stephen B. Helliwell ◽  
Michael N. Hall
Keyword(s):  
Cell Wall ◽  
Actin Cytoskeleton ◽  
Map Kinase ◽  
Cell Integrity ◽  
Exchange Factor ◽  
Downstream Effectors ◽  
Mitogen Activated Protein ◽  
Kinase Cascade ◽  
Map Kinase Pathway ◽  
Kinase Pathway

ABSTRACT The PKC1-associated mitogen-activated protein (MAP) kinase pathway of Saccharomyces cerevisiae regulates cell integrity by controlling the actin cytoskeleton and cell wall synthesis. Activation of PKC1 occurs via the GTPase RHO1 and the kinase pair PKH1 and PKH2. Here we report that YPK1 and YPK2, an essential pair of homologous kinases and proposed downstream effectors of PKH and sphingolipids, are also regulators of the PKC1-controlled MAP kinase cascade. ypk mutants display random distribution of the actin cytoskeleton and severely reduced activation of the MAP kinase MPK1. Upregulation of the RHO1 GTPase switch or the PKC1 effector MAP kinase pathway suppresses the growth and actin defects of ypk cells. ypk lethality is also suppressed by overexpression of an uncharacterized gene termed TUS1. TUS1 is a novel RHO1 exchange factor that contributes to cell wall integrity-mediated modulation of RHO1 activity. Thus, TUS1 and the YPKs add to the growing complexity of RHO1 and PKC1 regulation in the cell integrity signaling pathway. Furthermore, our findings suggest that the YPKs are a missing link between sphingolipid signaling and the cell integrity pathway.

Sign in / Sign up

Export Citation Format

Share Document