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Search Results to David E Levin, PhD

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Research Expertise & Professional Interests Expertise in stress signaling and cell wall biogenesis in fungi. We use baker’s yeast, Saccharomyces cerevisiae, as a model genetic organism in which to study the molecular mechanisms of stress signaling. The biomedical relevance of our work is twofold. First, we seek to identify novel aspects of signal transduction that are evolutionarily conserved with humans and therefore tell us something about our own biology that may be useful in the treatment of disease. Second, when we identify aspects or components of signaling pathways that are unique to fungi, these often represent potential targets for antifungal drug discovery. One project concerns the dissection of the Cell Wall Integrity (CWI) signaling pathway, which detects and responds to cell wall stress during growth and morphogenesis. Because animal cells lack cell walls, this structure is an attractive drug target in fungal pathogens. Disruption of the fungal cell wall results in cell lysis. The CWI pathway uses a set of cell surface sensors that are connected to a small G-protein, which activates signaling through a MAP kinase cascade. We have found in recent studies that, in addition to its catalytic activity as a protein kinase, the MAP kinase of the CWI pathway has a previously unknown non-catalytic function in the control of transcription elongation. We found that the basal expression of many stress-induced genes is minimized through premature transcription termination (or attenuation) shortly after initiation. The non-catalytic function of the MAP kinase under stress conditions is to prevent transcription attenuation through its interaction with the transcription elongation complex. This mechanism appears to be evolutionarily conserved in humans and may offer a new approach to therapeutic gene silencing. A second project exploits the need of fungal cells to maintain osmotic homeostasis through the regulation of intracellular glycerol concentration. We have identified a pair of genes, named RGC1 and RGC2 (for Regulators of the Glycerol Channel) whose function is to control the activity of the Fps1 glycerol channel, which acts as a plasma membrane vent that decreases turgor pressure by releasing glycerol from the cell. The fungal kingdom is replete with members of the Rgc family of proteins, but they have not been found in metazoan organisms. For this reason, and because mutants in these genes undergo cell lysis as a result of excess turgor pressure, the Rgc proteins may be suitable antifungal targets. Current studies are centered on understanding the biochemical function of Rgc1/2 and their mode of regulation in response to osmotic stress.

One or more keywords matched the following items that are connected to Levin, David

Item TypeName
Concept Protein Kinase C
Concept Protein Kinases
Concept Protein-Tyrosine Kinases
Concept Protein-Serine-Threonine Kinases
Concept Calcium-Calmodulin-Dependent Protein Kinases
Concept Mitogen-Activated Protein Kinases
Concept Mitogen-Activated Protein Kinase Kinases
Concept Mitogen-Activated Protein Kinase 7
Concept Checkpoint Kinase 2
Academic Article The proliferation of MAP kinase signaling pathways in yeast.
Academic Article The protein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response.
Academic Article Dissecting the protein kinase C/MAP kinase signalling pathway of Saccharomyces cerevisiae.
Academic Article Evidence against the existence of the purported Saccharomyces cerevisiae PKC2 gene.
Academic Article Saccharomyces cerevisiae PKC1 encodes a protein kinase C (PKC) homolog with a substrate specificity similar to that of mammalian PKC.
Academic Article A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1-mediated pathway.
Academic Article A pair of putative protein kinase genes (YPK1 and YPK2) is required for cell growth in Saccharomyces cerevisiae.
Academic Article A second osmosensing signal transduction pathway in yeast. Hypotonic shock activates the PKC1 protein kinase-regulated cell integrity pathway.
Academic Article Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog.
Academic Article A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C.
Academic Article MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C.
Academic Article A conserved kinase cascade for MAP kinase activation in yeast.
Academic Article Identification of yeast Rho1p GTPase as a regulatory subunit of 1,3-beta-glucan synthase.
Academic Article Dynamics and organization of MAP kinase signal pathways.
Academic Article Activation of yeast protein kinase C by Rho1 GTPase.
Academic Article A role for the Pkc1 MAP kinase pathway of Saccharomyces cerevisiae in bud emergence and identification of a putative upstream regulator.
Academic Article Temperature-induced expression of yeast FKS2 is under the dual control of protein kinase C and calcineurin.
Academic Article Genome-wide analysis of gene expression regulated by the yeast cell wall integrity signalling pathway.
Academic Article Wsc1 and Mid2 are cell surface sensors for cell wall integrity signaling that act through Rom2, a guanine nucleotide exchange factor for Rho1.
Academic Article Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase.
Academic Article HTL1 encodes a novel factor that interacts with the RSC chromatin remodeling complex in Saccharomyces cerevisiae.
Academic Article Mutants in the S. cerevisiae PKC1 gene display a cell cycle-specific osmotic stability defect.
Academic Article Cell wall integrity signaling in Saccharomyces cerevisiae.
Academic Article Dissecting the transcriptional activation function of the cell wall integrity MAP kinase.
Academic Article A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle.
Academic Article Yeast Mpk1 mitogen-activated protein kinase activates transcription through Swi4/Swi6 by a noncatalytic mechanism that requires upstream signal.
Academic Article Identification of positive regulators of the yeast fps1 glycerol channel.
Academic Article Mechanism of Mpk1 mitogen-activated protein kinase binding to the Swi4 transcription factor and its regulation by a novel caffeine-induced phosphorylation.
Academic Article Yeast Mpk1 cell wall integrity mitogen-activated protein kinase regulates nucleocytoplasmic shuttling of the Swi6 transcriptional regulator.
Academic Article Mpk1 MAPK association with the Paf1 complex blocks Sen1-mediated premature transcription termination.
Academic Article A putative protein kinase gene (kin1+) is important for growth polarity in Schizosaccharomyces pombe.
Academic Article Two yeast genes that encode unusual protein kinases.
Academic Article MAPK Hog1 closes the S. cerevisiae glycerol channel Fps1 by phosphorylating and displacing its positive regulators.
Academic Article Rgc2 Regulator of Glycerol Channel Fps1 Functions as a Homo- and Heterodimer with Rgc1.
Academic Article Intracellular mechanism by which arsenite activates the yeast stress MAPK Hog1.

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