scholarly journals Sck1 Negatively Regulates Gpa2-Mediated Glucose Signaling in Schizosaccharomyces pombe

2013 ◽  
Vol 13 (2) ◽  
pp. 202-208 ◽  
Author(s):  
Dayna K. Mudge ◽  
Fan Yang ◽  
Brian M. Currie ◽  
James M. Kim ◽  
Kelly Yeda ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Schizosaccharomyces Pombe ◽  
G Protein ◽  
Free Form ◽  
Slight Reduction ◽  
Content Type ◽  
Glucose Signaling ◽  
Extracellular Glucose ◽  
The One ◽  
Two Hybrid

ABSTRACTSchizosaccharomyces pombedetects extracellular glucose via a G protein-mediated cyclic AMP (cAMP)-signaling pathway activating protein kinase A (PKA) and regulating transcription of genes involved in metabolism and sexual development. In this pathway, Gpa2 Gα binds to and activates adenylyl cyclase in response to glucose detection by the Git3 G protein-coupled receptor. Using a two-hybrid screen to identify extrinsic regulators of Gpa2, we isolated a clone that expresses codons 471 to 696 of the Sck1 kinase, which appears to display a higher affinity for Gpa2K270E-activated Gα relative to Gpa2+Gα. Deletion ofsck1+or mutational inactivation of the Sck1 kinase produces phenotypes reflecting increased PKA activity in strains expressing Gpa2+or Gpa2K270E, suggesting that Sck1 negatively regulates PKA activation through Gpa2. In contrast to the Gpa2K270EGDP-GTP exchange rate mutant, GTPase-defective Gpa2R176Hweakly binds Sck1 in the two-hybrid screen and a deletion ofsck1+in a Gpa2R176Hstrain confers phenotypes consistent with a slight reduction in PKA activity. Finally, deletingsck1+in agpa2Δ strain results in phenotypes consistent with a second role for Sck1 acting in parallel with PKA. In addition to this parallel role with PKA, our data suggest that Sck1 negatively regulates Gpa2, possibly targeting the nucleotide-free form of the protein that may expose the one and only AKT/PKB consensus site in Gpa2 for Sck1 to bind. This dual role for Sck1 may allowS. pombeto produce distinct biological responses to glucose and nitrogen starvation signals that both activate the Wis1-Spc1/StyI stress-activated protein kinase (SAPK) pathway.

scholarly journals Glycolysis Controls Plasma Membrane Glucose Sensors To Promote Glucose Signaling in Yeasts

2014 ◽  
Vol 35 (4) ◽  
pp. 747-757 ◽  
Author(s):  
Amélie Cairey-Remonnay ◽  
Julien Deffaud ◽  
Micheline Wésolowski-Louvel ◽  
Marc Lemaire ◽  
Alexandre Soulard
Keyword(s):  
Signaling Pathway ◽  
Glucose Sensor ◽  
Kluyveromyces Lactis ◽  
Glucose Sensors ◽  
Content Type ◽  
Glucose Signaling ◽  
Extracellular Glucose ◽  
Glucose Accumulation ◽  
The Stability ◽  
Intracellular Glucose

Sensing of extracellular glucose is necessary for cells to adapt to glucose variation in their environment. In the respiratory yeastKluyveromyces lactis, extracellular glucose controls the expression of major glucose permease geneRAG1through a cascade similar to theSaccharomyces cerevisiaeSnf3/Rgt2/Rgt1 glucose signaling pathway. This regulation depends also on intracellular glucose metabolism since we previously showed that glucose induction of theRAG1gene is abolished in glycolytic mutants. Here we show that glycolysis regulatesRAG1expression through theK. lactisRgt1 (KlRgt1) glucose signaling pathway by targeting the localization and probably the stability of Rag4, the single Snf3/Rgt2-type glucose sensor ofK. lactis. Additionally, the control exerted by glycolysis on glucose signaling seems to be conserved inS. cerevisiae. This retrocontrol might prevent yeasts from unnecessary glucose transport and intracellular glucose accumulation.

scholarly journals Noncanonical G-Protein-Dependent Modulation of Osteoclast Differentiation and Bone Resorption Mediated by Pasteurella multocida Toxin

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Julia Strack ◽  
Hannah Heni ◽  
Ralf Gilsbach ◽  
Lutz Hein ◽  
Klaus Aktories ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Bone Resorption ◽  
G Protein ◽  
G Proteins ◽  
Pasteurella Multocida ◽  
Osteoclast Differentiation ◽  
Mitogen Activated Protein Kinase ◽  
Atrophic Rhinitis ◽  
Heterotrimeric G Proteins ◽  
Content Type

ABSTRACT Pasteurella multocida toxin (PMT) induces atrophic rhinitis in animals, which is characterized by a degradation of nasal turbinate bones, indicating an effect of the toxin on bone cells such as osteoblasts and osteoclasts. The underlying molecular mechanism of PMT was defined as a persistent activation of heterotrimeric G proteins by deamidation of a specific glutamine residue. Here, we show that PMT acts directly on osteoclast precursor cells such as bone marrow-derived CD14+ monocytes and RAW246.7 cells to induce osteoclastogenesis as measured by expression of osteoclast-specific markers such as tartrate-resistant acid phosphatase and bone resorption activity. Treatment performed solely with PMT stimulates osteoclast differentiation, showing a receptor activator of nuclear factor-κB ligand (RANKL)-independent action of the toxin. The underlying signal transduction pathway was defined as activation of the heterotrimeric G proteins Gαq/11 leading to the transactivation of Ras and the mitogen-activated protein kinase pathway. Gαq/11 transactivates Ras via its effector phospholipase Cβ-protein kinase C (PKC) involving proline-rich tyrosine kinase 2 (Pyk2). PMT-induced activation of the mitogen-activated protein kinase pathway results in stimulation of the osteoclastogenic transcription factors AP-1, NF-κB, and NFATc1. In addition, Ca2+-dependent calcineurin activation of NFAT is crucial for PMT-induced osteoclastogenesis. The data not only elucidate a rationale for PMT-dependent bone loss during atrophic rhinitis but also highlight a noncanonical, G-protein-dependent pathway toward bone resorption that is distinct from the RANKL-RANK pathway but mimics it. We define heterotrimeric G proteins as as-yet-underestimated entities/players in the maturation of osteoclasts which might be of pharmacological relevance. IMPORTANCE Pasteurella multocida toxin (PMT) induces degradation of nasal turbinate bones, leading to the syndrome of atrophic rhinitis. Recently, the molecular mechanism and substrate specificity of PMT were identified. The toxin activates heterotrimeric G proteins by a covalent modification. However, the mechanism by which PMT induces bone degradation is poorly understood. Our report demonstrates a direct effect of PMT on osteoclast precursor cells, leading to maturation of bone-degrading osteoclasts. Interestingly, PMT stimulates osteoclastogenesis independently of the cytokine RANKL, which is a key factor in induction of osteoclast differentiation. This implicates a noncanonical osteoclastogenic signaling pathway induced by PMT. The elucidated Gαq/11-dependent osteoclastogenic signal transduction pathway ends in osteoclastogenic NFAT signaling. The noncanonical, heterotrimeric G protein-dependent osteoclast differentiation process may be of pharmacological relevance, as members of this pathway are highly druggable. In particular, modulation of G protein-coupled receptor activity in osteoclast progenitors by small molecules might be of specific interest.

scholarly journals GPR11, a Putative Seven-Transmembrane G Protein-Coupled Receptor, Controls Zoospore Development and Virulence of Phytophthora sojae

2009 ◽  
Vol 9 (2) ◽  
pp. 242-250 ◽  
Author(s):  
Yonglin Wang ◽  
Aining Li ◽  
Xiaoli Wang ◽  
Xin Zhang ◽  
Wei Zhao ◽  
...  
Keyword(s):  
G Protein ◽  
Hyphal Growth ◽  
Phytophthora Sojae ◽  
G Protein Coupled Receptors ◽  
Yeast Two Hybrid ◽  
Content Type ◽  
Signaling Mechanisms ◽  
G Protein Coupled ◽  
Two Hybrid ◽  
Receptor Family

ABSTRACT G protein-coupled receptors (GPCRs) represent a large receptor family involved in a broad spectrum of cell signaling. To understand signaling mechanisms mediated by GPCRs in Phytophthora sojae, we identified and characterized the PsGPR11 gene, which encodes a putative seven-transmembrane GPCR. An expression analysis revealed that PsGPR11 was differentially expressed during asexual development. The highest expression level occurred in zoospores and was upregulated during early infection. PsGPR11-deficienct transformants were obtained by gene silencing strategies. Silenced transformants exhibited no differences in hyphal growth or morphology, sporangium production or size, or mating behavior. However, the release of zoospores from sporangia was severely impaired in the silenced transformants, and about 50% of the sporangia did not completely release their zoospores. Zoospore encystment and germination were also impaired, and zoospores of the transformants lost their pathogenicity to soybean. In addition, no interaction was observed between PsGPR11 and PsGPA1 with a conventional yeast two-hybrid assay, and the transcriptional levels of some genes which were identified as being negatively regulated by PsGPA1 were not clearly altered in PsGPR11-silenced mutants. These results suggest that PsGPR11-mediated signaling controls P. sojae zoospore development and virulence through the pathways independent of G protein.

scholarly journals Glucose sensing via the protein kinase A pathway in Schizosaccharomyces pombe

2005 ◽  
Vol 33 (1) ◽  
pp. 257-260 ◽  
Author(s):  
C.S. Hoffman
Keyword(s):  
Protein Kinase ◽  
Adenylate Cyclase ◽  
Schizosaccharomyces Pombe ◽  
Protein Kinase A ◽  
G Protein ◽  
Glucose Sensing ◽  
Independent Manner ◽  
Camp Phosphodiesterase ◽  
Camp Pathway ◽  
Kinase A

The fission yeast Schizosaccharomyces pombe primarily detects glucose via a cAMP-signalling pathway. Components of this pathway include the Git3 G-protein-coupled receptor and a heterotrimeric G-protein, from which the Gpa2 Gα subunit activates adenylate cyclase (Git2/Cyr1). Three additional proteins, Git1, Git7 and Git10 are required to generate a cAMP response even in a strain expressing an activated form of Gpa2, which is capable of bypassing the loss of the GPCR and Gβγ dimer. Therefore, Git1, Git7 and Git10 either act in a G-protein-independent manner or are required to stabilize or assemble a functional signalling complex. Although prior data suggested that the Cgs2 cAMP phosphodiesterase (PDE) does not regulate the cAMP response, we now have evidence that along with adenylate cyclase regulation, PDE activation is important for limiting the response to glucose. Finally, regulation of protein kinase A activation appears to involve both traditional post-translational regulation of the function of the components of the cAMP pathway and glucose-dependent transcriptional regulation of some of these cAMP pathway genes.

scholarly journals The SWI/SNF KlSnf2 Subunit Controls the Glucose Signaling Pathway To Coordinate Glycolysis and Glucose Transport in Kluyveromyces lactis

2012 ◽  
Vol 11 (11) ◽  
pp. 1382-1390 ◽  
Author(s):  
Pascale Cotton ◽  
Alexandre Soulard ◽  
Micheline Wésolowski-Louvel ◽  
Marc Lemaire
Keyword(s):  
Signaling Pathway ◽  
Glucose Transport ◽  
Chromatin Remodeling ◽  
Kluyveromyces Lactis ◽  
Content Type ◽  
Glucose Signaling ◽  
Helix Loop Helix ◽  
Reverse Transcription Quantitative Pcr ◽  
Extracellular Glucose ◽  
Transcriptional Effect

ABSTRACTInKluyveromyces lactis, the expression of the major glucose permease geneRAG1is controlled by extracellular glucose through a signaling cascade similar to theSaccharomyces cerevisiaeSnf3/Rgt2/Rgt1 pathway. We have identified a key component of theK. lactisglucose signaling pathway by characterizing a new mutation,rag20-1, which impairs the regulation ofRAG1and hexokinaseRAG5genes by glucose. Functional complementation of therag20-1mutation identified theKlSNF2gene, which encodes a protein 59% identical toS. cerevisiaeSnf2, the major subunit of the SWI/SNF chromatin remodeling complex. Reverse transcription-quantitative PCR and chromatin immunoprecipitation analyses confirmed that the KlSnf2 protein binds toRAG1andRAG5promoters and promotes the recruitment of the basic helix-loop-helix Sck1 activator. Besides this transcriptional effect, KlSnf2 is also implicated in the glucose signaling pathway by controlling Sms1 and KlRgt1 posttranscriptional modifications. When KlSnf2 is absent, Sms1 is not degraded in the presence of glucose, leading to constitutiveRAG1gene repression by KlRgt1. Our work points out the crucial role played by KlSnf2 in the regulation of glucose transport and metabolism inK. lactis, notably, by suggesting a link between chromatin remodeling and the glucose signaling pathway.

How Phillips saw the light

2020 ◽  
Vol 36 (8) ◽  
pp. 29-31
Keyword(s):  
Design Methodology ◽  
Reading Time ◽  
Daily Basis ◽  
Business World ◽  
Content Type ◽  
Freak Show ◽  
The World ◽  
Pertinent Information ◽  
The One ◽  
Practical Implications

Purpose Reviews the latest management developments across the globe and pinpoints practical implications from cutting-edge research and case studies. Design/methodology/approach This briefing is prepared by an independent writer who adds their own impartial comments and places the articles in context. Findings The problem with developing a reputation of being something of an oracle in the business world is that all of a sudden, everyone expects you to pull off the trick of interpreting the future on a daily basis. Like a freak show circus act or one-hit wonder pop singer, people expect you to perform when they see you, and they expect you to perform the thing that made you famous, even if it is the one thing in the world you don’t want to do. And when you fail to deliver on these heightened expectations, you are dismissed as a one trick pony, however good that trick is in the first place. Originality/value The briefing saves busy executives and researchers hours of reading time by selecting only the very best, most pertinent information and presenting it in a condensed and easy-to-digest format.

PROMETHEE-based ranking of project managers based on the five personality traits

Kybernetes ◽  
2019 ◽  
Vol 49 (4) ◽  
pp. 1083-1102
Author(s):  
Georgios N. Aretoulis ◽  
Jason Papathanasiou ◽  
Fani Antoniou
Keyword(s):  
Personality Traits ◽  
Questionnaire Survey ◽  
Multicriteria Decision Making ◽  
Project Managers ◽  
Preference Ranking ◽  
Infrastructure Projects ◽  
Public Infrastructure ◽  
Content Type ◽  
The One ◽  
Selection Of

Purpose This paper aims to rank and identify the most efficient project managers (PMs) based on personality traits, using Preference Ranking Organization METHod for Enrichment Evaluations (PROMETHEE) methodology. Design/methodology/approach The proposed methodology relies on the five personality traits. These were used as the selection criteria. A questionnaire survey among 82 experienced engineers was used to estimate the required weights per personality trait. A second two-part questionnaire survey aimed at recording the PMs profile and assess the performance of personality traits per PM. PMs with the most years of experience are selected to be ranked through Visual PROMETHEE. Findings The findings suggest that a competent PM is the one that scores low on the “Neuroticism” trait and high especially on the “Conscientiousness” trait. Research limitations/implications The research applied a psychometric test specifically designed for Greek people. Furthermore, the proposed methodology is based on the personality characteristics to rank the PMs and does not consider the technical skills. Furthermore, the type of project is not considered in the process of ranking PMs. Practical implications The findings could contribute in the selection of the best PM that maximizes the project team’s performance. Social implications Improved project team communication and collaboration leading to improved project performance through better communication and collaboration. This is an additional benefit for the society, especially in the delivery of public infrastructure projects. A lot of public infrastructure projects deviate largely as far as cost and schedule is concerned and this is an additional burden for public and society. Proper project management through efficient PMs would save people’s money and time. Originality/value Identification of the best PMbased on a combination of multicriteria decision-making and psychometric tests, which focus on personality traits.

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