scholarly journals The High Osmolarity Glycerol (HOG) Pathway Functions in Osmosensing, Trap Morphogenesis and Conidiation of the Nematode-Trapping Fungus Arthrobotrys oligospora

2020 ◽  
Vol 6 (4) ◽  
pp. 191
Author(s):  
Chih-Yen Kuo ◽  
Sheng-An Chen ◽  
Yen-Ping Hsueh
Keyword(s):  
Critical Role ◽  
Fungal Species ◽  
Nutrient Sensing ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Arthrobotrys Oligospora ◽  
High Osmolarity ◽  
Cellular Processes ◽  
Predation Efficiency ◽  
Mitogen Activated Protein

Hog1, a mitogen-activated protein kinase (MAPK), has been identified in diverse fungal species, and it regulates various cellular processes, such as osmoadaptation, nutrient-sensing, and pathogenesis. However, the roles that Hog1 plays in nematode-trapping fungi were previously unclear. Here, we characterized orthologs of Saccharomyces cerevisiae Hog1 and membrane mucin Msb2 in the nematode-trapping fungus Arthrobotrys oligospora. We generated gene deletion mutants of HOG1 and MSB2 in A. oligospora, and characterized their roles in osmosensing, growth, and trap morphogenesis. We found that both hog1 and msb2 mutants were highly sensitive to high osmolarity. Predation analyses further revealed that hog1 and msb2 deletion caused a reduction in trap formation and predation efficiency. Furthermore, HOG1 is required for conidiation in A. oligospora, demonstrating its critical role in this developmental pathway. In summary, this study demonstrated that the conserved Hog1 and Msb2 govern physiology, growth and development in the nematode-trapping fungus A. oligospora.

scholarly journals Msb2 Signaling Mucin Controls Activation of Cek1 Mitogen-Activated Protein Kinase in Candida albicans

2009 ◽  
Vol 8 (8) ◽  
pp. 1235-1249 ◽  
Author(s):  
Elvira Román ◽  
Fabien Cottier ◽  
Joachim F. Ernst ◽  
Jesús Pla
Keyword(s):  
Cell Wall ◽  
Candida Albicans ◽  
Protein Kinase ◽  
Osmotic Shock ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
High Osmolarity ◽  
Cell Wall Biogenesis ◽  
Solid Media ◽  
Mitogen Activated Protein

ABSTRACT We have characterized the role that the Msb2 protein plays in the fungal pathogen Candida albicans by the use of mutants defective in the putative upstream components of the HOG pathway. Msb2, in cooperation with Sho1, controls the activation of the Cek1 mitogen-activated protein kinase under conditions that damage the cell wall, thus defining Msb2 as a signaling element of this pathway in the fungus. msb2 mutants display altered sensitivity to Congo red, caspofungin, zymolyase, or tunicamycin, indicating that this protein is involved in cell wall biogenesis. Msb2 (as well as Sho1 and Hst7) is involved in the transmission of the signal toward Cek1 mediated by the Cdc42 GTPase, as revealed by the use of activated alleles (Cdc42G12V) of this protein. msb2 mutants have a stronger defective invasion phenotype than sho1 mutants when tested on certain solid media that use mannitol or sucrose as a carbon source or under hypoxia. Interestingly, Msb2 contributes to growth under conditions of high osmolarity when both branches of the HOG pathway are altered, as triple ssk1 msb2 sho1 mutants (but not any single or double mutant) are osmosensitive. However, this phenomenon is independent of the presence of Hog1, as Hog1 phosphorylation, Hog1 translocation to the nucleus, and glycerol accumulation are not affected in this mutant following an osmotic shock. These results reveal essential functions in morphogenesis, invasion, cell wall biogenesis, and growth under conditions of high osmolarity for Msb2 in C. albicans and suggest the divergence and specialization of this signaling pathway in filamentous fungi.

scholarly journals Osmotic Stress-Induced Gene Expression in Saccharomyces cerevisiae Requires Msn1p and the Novel Nuclear Factor Hot1p

1999 ◽  
Vol 19 (8) ◽  
pp. 5474-5485 ◽  
Author(s):  
Martijn Rep ◽  
Vladimír Reiser ◽  
Ulrike Gartner ◽  
Johan M. Thevelein ◽  
Stefan Hohmann ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Osmotic Stress ◽  
Transcriptional Response ◽  
Mitogen Activated Protein Kinase ◽  
The Novel ◽  
Hog Pathway ◽  
High Osmolarity ◽  
Nuclear Factors ◽  
Mitogen Activated Protein ◽  
Protective Genes

ABSTRACT After a sudden shift to high osmolarity, Saccharomyces cerevisiae cells respond by transiently inducing the expression of stress-protective genes. Msn2p and Msn4p have been described as two transcription factors that determine the extent of this response. Inmsn2 msn4 mutants, however, many promoters still show a distinct rise in transcriptional activity upon osmotic stress. Here we describe two structurally related nuclear factors, Msn1p and a newly identified protein, Hot1p (for high-osmolarity-induced transcription), which are also involved in osmotic stress-induced transcription.hot1 single mutants are specifically compromised in the transient induction of GPD1 and GPP2, which encode enzymes involved in glycerol biosynthesis, and exhibit delayed glycerol accumulation after stress exposure. Similar to agpd1 mutation, a hot1 defect can rescue cells from inappropriately high HOG pathway activity. In contrast, Hot1p has little influence on the osmotic stress induction of CTT1, where Msn1p appears to play a more prominent role. Cells lacking Msn1p, Msn2p, Msn4p, and Hot1p are almost devoid of the short-term transcriptional response of the genes GPD1,GPP2, CTT1, and HSP12 to osmotic stress. Such cells also show a distinct reduction in the nuclear residence of the mitogen-activated protein kinase Hog1p upon osmotic stress. Thus, Hot1p and Msn1p may define an additional tier of transcriptional regulators that control responses to high-osmolarity stress.

scholarly journals Binding of the Extracellular Eight-Cysteine Motif of Opy2 to the Putative Osmosensor Msb2 Is Essential for Activation of the Yeast High-Osmolarity Glycerol Pathway

2015 ◽  
Vol 36 (3) ◽  
pp. 475-487 ◽  
Author(s):  
Katsuyoshi Yamamoto ◽  
Kazuo Tatebayashi ◽  
Haruo Saito
Keyword(s):  
Conformational Changes ◽  
Disulfide Bonds ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Content Type ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
Cysteine Motif ◽  
Mitogen Activated Protein ◽  
A Site

To adapt to environmental high osmolarity, the budding yeastSaccharomyces cerevisiaeactivates the Hog1 mitogen-activated protein kinase, which regulates diverse osmoadaptive responses. Hog1 is activated through the high-osmolarity glycerol (HOG) pathway, which consists of independent upstream signaling routes termed the SLN1 branch and the SHO1 branch. Here, we report that the extracellular cysteine-rich (CR) domain of the transmembrane-anchor protein Opy2 binds to the Hkr1-Msb2 homology (HMH) domain of the putative osmosensor Msb2 and that formation of the Opy2-Msb2 complex is essential for osmotic activation of Hog1 through the MSB2 subbranch of the SHO1 branch. By analyzing the phenotypes of mutants with Opy2 cysteine-to-alanine mutations, we deduced that the CR domain forms four intramolecular disulfide bonds. To probe for the potential induction of conformational changes in the Opy2-Msb2 complex by osmostress, we constructed mutants with a site-specific Cys-to-Ala mutation of the Opy2 CR domain and mutants with a Cys substitution of the Msb2 HMH domain. Each of these mutants had a reduced cysteine. These mutants were then combinatorially cross-linked using chemical cross-linkers of different lengths. Cross-linking between Opy2 Cys48 and Msb2 Cys1023 was sensitive to osmotic changes, suggesting that osmostress induced a conformational change. We therefore propose that the Opy2-Msb2 complex might serve as an osmosensor.

scholarly journals Unique and Redundant Roles for HOG MAPK Pathway Components as Revealed by Whole-Genome Expression Analysis

2004 ◽  
Vol 15 (2) ◽  
pp. 532-542 ◽  
Author(s):  
Sean M. O'Rourke ◽  
Ira Herskowitz
Keyword(s):  
Protein Kinase ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Whole Genome ◽  
Hog Pathway ◽  
General Stress Response ◽  
High Osmolarity ◽  
Genome Expression ◽  
Mitogen Activated Protein ◽  
Whole Genome Expression

The Saccharomyces cerevisiae high osmolarity glycerol (HOG) mitogen-activated protein kinase pathway is required for osmoadaptation and contains two branches that activate a mitogen-activated protein kinase (Hog1) via a mitogen-activated protein kinase kinase (Pbs2). We have characterized the roles of common pathway components (Hog1 and Pbs2) and components in the two upstream branches (Ste11, Sho1, and Ssk1) in response to elevated osmolarity by using whole-genome expression profiling. Several new features of the HOG pathway were revealed. First, Hog1 functions during gene induction and repression, cross talk inhibition, and in governing the regulatory period. Second, the phenotypes of pbs2 and hog1 mutants are identical, indicating that the sole role of Pbs2 is to activate Hog1. Third, the existence of genes whose induction is dependent on Hog1 and Pbs2 but not on Ste11 and Ssk1 suggests that there are additional inputs into Pbs2 under our inducing conditions. Fourth, the two upstream pathway branches are not redundant: the Sln1-Ssk1 branch has a much more prominent role than the Sho1-Ste11 branch for activation of Pbs2 by modest osmolarity. Finally, the general stress response pathway and both branches of the HOG pathway all function at high osmolarity. These studies demonstrate that cells respond to increased osmolarity by using different signal transduction machinery under different conditions.

scholarly journals Cdc37p Is Required for Stress-Induced High-Osmolarity Glycerol and Protein Kinase C Mitogen-Activated Protein Kinase Pathway Functionality by Interaction with Hog1p and Slt2p (Mpk1p)

2007 ◽  
Vol 6 (3) ◽  
pp. 521-532 ◽  
Author(s):  
Patricija Hawle ◽  
Danielle Horst ◽  
Jan Paul Bebelman ◽  
Xiao Xian Yang ◽  
Marco Siderius ◽  
...  
Keyword(s):  
Cell Wall ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
High Osmolarity ◽  
High Osmolarity Glycerol ◽  
Kinase C ◽  
Mitogen Activated Protein

ABSTRACT The yeast Saccharomyces cerevisiae utilizes rapidly responding mitogen-activated protein kinase (MAPK) signaling cascades to adapt efficiently to a changing environment. Here we report that phosphorylation of Cdc37p, an Hsp90 cochaperone, by casein kinase 2 controls the functionality of two MAPK cascades in yeast. These pathways, the high-osmolarity glycerol (HOG) pathway and the cell integrity (protein kinase C) MAPK pathway, mediate adaptive responses to high osmotic and cell wall stresses, respectively. Mutation of the phosphorylation site Ser14 in Cdc37p renders cells sensitive to osmotic stress and cell wall perturbation by calcofluor white. We found that levels of the MAPKs Hog1p and Slt2p (Mpk1p) in cells are reduced in a cdc37-S14A mutant, and consequently downstream responses mediated by Hog1p and Slt2p are compromised. Furthermore, we present evidence that Hog1p and Slt2p both interact in a complex with Cdc37p in vivo, something that has not been reported previously. The interaction of Hsp90, Slt2p, and Hog1p with Cdc37p depends on the phosphorylation status of Cdc37p. In fact, our biochemical data show that the osmosensitive phenotype of the cdc37-S14A mutant is due to the loss of the interaction between Cdc37p, Hog1p, and Hsp90. Likewise, during cell wall stress, the interaction of Slt2p with Cdc37p and Hsp90 is crucial for Slt2p-dependent downstream responses, such as the activation of the transcription factor Rlm1p. Interestingly, phosphorylated Slt2p, but not phosphorylated Hog1p, has an increased affinity for Cdc37p. Together these observations suggest that Cdc37p acts as a regulator of MAPK signaling.

scholarly journals Kinase Activity-dependent Nuclear Export Opposes Stress-induced Nuclear Accumulation and Retention of Hog1 Mitogen-activated Protein Kinase in the Budding Yeast Saccharomyces cerevisiae

1999 ◽  
Vol 10 (4) ◽  
pp. 1147-1161 ◽  
Author(s):  
Vladimı́r Reiser ◽  
Helmut Ruis ◽  
Gustav Ammerer
Keyword(s):  
Protein Kinase ◽  
Nuclear Export ◽  
Kinase Activity ◽  
De Novo ◽  
Budding Yeast ◽  
Mitogen Activated Protein Kinase ◽  
Nuclear Accumulation ◽  
Hog Pathway ◽  
High Osmolarity ◽  
Mitogen Activated Protein

Budding yeast adjusts to increases in external osmolarity via a specific mitogen-activated protein kinase signal pathway, the high-osmolarity glycerol response (HOG) pathway. Studies with a functional Hog1–green fluorescent protein (GFP) fusion reveal that even under nonstress conditions the mitogen-activated protein kinase Hog1 cycles between cytoplasmic and nuclear compartments. The basal distribution of the protein seems independent of its activator, Pbs2, and independent of its phosphorylation status. Upon osmotic challenge, the Hog1–GFP fusion becomes rapidly concentrated in the nucleus from which it is reexported after return to an iso-osmotic environment or after adaptation to high osmolarity. The preconditions and kinetics of increased nuclear localization correlate with those found for the dual phosphorylation of Hog1–GFP. The duration of Hog1 nuclear residence is modulated by the presence of the general stress activators Msn2 and Msn4. Reexport of Hog1 to the cytoplasm does not require de novo protein synthesis but depends on Hog1 kinase activity. Thus, at least three different mechanisms contribute to the intracellular distribution pattern of Hog1: phosphorylation-dependent nuclear accumulation, retention by nuclear targets, and a kinase-induced export.

scholarly journals Role of p90RSK in Kidney and Other Diseases

2019 ◽  
Vol 20 (4) ◽  
pp. 972 ◽  
Author(s):  
Ling Lin ◽  
Samantha White ◽  
Kebin Hu
Keyword(s):  
Kidney Diseases ◽  
Critical Role ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Processes ◽  
Downstream Effector ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Selection Of

The 90 kDa ribosomal s6 kinases (RSKs) are a group of serine/threonine kinases consisting of 4 RSK isoforms (RSK1-4), of which RSK1 is also designated as p90RSK. p90RSK plays an important role in the Ras-mitogen-activated protein kinase (MAPK) signalling cascade and is the direct downstream effector of Ras-extracellular signal-regulated kinase (ERK1/2) signalling. ERK1/2 activation directly phosphorylates and activates p90RSK, which, in turn, activates various signalling events through selection of different phosphorylation substrates. Upregulation of p90RSK has been reported in numerous human diseases. p90RSK plays an important role in the regulation of diverse cellular processes. Thus, aberrant activation of p90RSK plays a critical role in the pathogenesis of organ dysfunction and damage. In this review, we focus on the current understanding of p90RSK functions and roles in the development and progression of kidney diseases. Roles of p90RSK, as well as other RSKs, in cardiovascular disorders and cancers are also discussed.

scholarly journals Phosphothreonine Lyase Promotes p65 Degradation in a Mitogen-Activated Protein Kinase/Mitogen- and Stress-Activated Protein Kinase 1-Dependent Manner

2018 ◽  
Vol 87 (1) ◽  
Author(s):  
Mingyu Hou ◽  
Wenhui Wang ◽  
Feizi Hu ◽  
Yuanxing Zhang ◽  
Dahai Yang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Pathogenic Bacteria ◽  
Critical Role ◽  
Nuclear Factor Κb ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Content Type ◽  
Catalytic Active Site ◽  
Mitogen Activated Protein

ABSTRACT Bacterial phosphothreonine lyases have been identified to be type III secretion system (T3SS) effectors that irreversibly dephosphorylate host mitogen-activated protein kinase (MAPK) signaling to promote infection. However, the effects of phosphothreonine lyase on nuclear factor κB (NF-κB) signaling remain largely unknown. In this study, we detected significant phosphothreonine lyase-dependent p65 degradation during Edwardsiella piscicida infection in macrophages, and this degradative effect was blocked by the protease inhibitor MG132. Further analysis revealed that phosphothreonine lyase promotes the dephosphorylation and ubiquitination of p65 by inhibiting the phosphorylation of mitogen- and stress-activated protein kinase-1 (MSK1) and by inhibiting the phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2), p38α, and c-Jun N-terminal kinase (JNK). Moreover, we revealed that the catalytic active site of phosphothreonine lyase plays a critical role in regulating the MAPK-MSK1-p65 signaling axis. Collectively, the mechanism described here expands our understanding of the pathogenic effector in not only regulating MAPK signaling but also regulating p65. These findings uncover a new mechanism by which pathogenic bacteria overcome host innate immunity to promote pathogenesis.

scholarly journals Mitogen-Activated Protein Kinase Hog1 Mediates Adaptation to G1 Checkpoint Arrest during Arsenite and Hyperosmotic Stress

2008 ◽  
Vol 7 (8) ◽  
pp. 1309-1317 ◽  
Author(s):  
Iwona Migdal ◽  
Yulia Ilina ◽  
Markus J. Tamás ◽  
Robert Wysocki
Keyword(s):  
Cell Cycle ◽  
Protein Kinase ◽  
Cell Cycle Arrest ◽  
Kinase Inhibitor ◽  
Hyperosmotic Stress ◽  
Mitogen Activated Protein Kinase ◽  
Hog Pathway ◽  
Cycle Arrest ◽  
Mitogen Activated Protein

ABSTRACT Cells slow down cell cycle progression in order to adapt to unfavorable stress conditions. Yeast (Saccharomyces cerevisiae) responds to osmotic stress by triggering G1 and G2 checkpoint delays that are dependent on the mitogen-activated protein kinase (MAPK) Hog1. The high-osmolarity glycerol (HOG) pathway is also activated by arsenite, and the hog1Δ mutant is highly sensitive to arsenite, partly due to increased arsenite influx into hog1Δ cells. Yeast cell cycle regulation in response to arsenite and the role of Hog1 in this process have not yet been analyzed. Here, we found that long-term exposure to arsenite led to transient G1 and G2 delays in wild-type cells, whereas cells that lack the HOG1 gene or are defective in Hog1 kinase activity displayed persistent G1 cell cycle arrest. Elevated levels of intracellular arsenite and “cross talk” between the HOG and pheromone response pathways, observed in arsenite-treated hog1Δ cells, prolonged the G1 delay but did not cause a persistent G1 arrest. In contrast, deletion of the SIC1 gene encoding a cyclin-dependent kinase inhibitor fully suppressed the observed block of G1 exit in hog1Δ cells. Moreover, the Sic1 protein was stabilized in arsenite-treated hog1Δ cells. Interestingly, Sic1-dependent persistent G1 arrest was also observed in hog1Δ cells during hyperosmotic stress. Taken together, our data point to an important role of the Hog1 kinase in adaptation to stress-induced G1 cell cycle arrest.

scholarly journals Elucidation on Predominant Pathways Involved in the Differentiation and Mineralization of Odontoblast-Like Cells by Selective Blockade of Mitogen-Activated Protein Kinases

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Jia Tang ◽  
Takashi Saito
Keyword(s):  
Cell Differentiation ◽  
Signaling Pathway ◽  
Critical Role ◽  
Mapk Signaling ◽  
Significant Inhibition ◽  
Mitogen Activated Protein Kinase ◽  
Alizarin Red ◽  
Selective Blockade ◽  
Alp Activity ◽  
Mitogen Activated Protein

Aim. To analyze the effect of three mitogen-activated protein kinase (MAPK) inhibitors, namely, SB202190 (p38 inhibitor), SP600125 (JNK inhibitor), and PD98059 (ERK inhibitor) in Dex-stimulated MDPC-23 cell differentiation and mineralization. Methods. Experiment was divided into five groups, control (cells without Dex and inhibitors treatment), Dex (cells with Dex treatment but without inhibitors), Dex + SB202190, Dex + SP600125, and Dex + PD98059. Cell differentiation was assessed by alkaline phosphatase (ALP) activity assay and real time RT-PCR. Cell mineralization was investigated by alizarin red staining. Results. Exposure to SB202190 (20 μM) significantly decreased the mineral deposition in Dex-treated cells as demonstrated by alizarin red staining. Treatment of SP600125 (20 μM) attenuated the mineralization as well, albeit at a lower degree as compared to SB202190 (20 μM). Similarly, SB202190 (20 μM) completely abrogated the ALP activity stimulated by Dex at six days in culture, while no changes were observed with regard to ALP activity in SP600125 (20 μM) and PD98059 (20 μM) treated cells. The upregulation of bone sialoprotein (BSP), ALP, and osteopontin (OPN) in Dex challenged cells was completely inhibited by SB202190. Conclusion. Blockade of p38-MAPK signaling pathway resulted in significant inhibition of ALP activity, mineralization, and downregulation of osteogenic markers. The data implicated that p38 signaling pathway plays a critical role in the regulation of MDPC-23 cells differentiation and mineralization.

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