ingest cdrApp 2017-07-05T20:12:38.282Z d36eae88-cb6b-42c1-ba08-197eadfa9868 modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-07-05T20:28:01.871Z Setting exclusive relation modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-07-05T20:28:10.454Z Setting exclusive relation addDatastream MD_TECHNICAL fedoraAdmin 2017-07-05T20:28:18.987Z Adding technical metadata derived by FITS modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-07-05T20:28:35.474Z Setting exclusive relation addDatastream MD_FULL_TEXT fedoraAdmin 2017-07-05T20:28:44.679Z Adding full text metadata extracted by Apache Tika modifyDatastreamByValue RELS-EXT fedoraAdmin 2017-07-05T20:29:00.777Z Setting exclusive relation modifyDatastreamByValue RELS-EXT cdrApp 2017-07-06T11:39:06.066Z Setting exclusive relation modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-04T15:47:03.748Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-25T10:10:21.124Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-01-27T10:18:40.158Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-03-14T07:06:39.225Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-05-17T18:37:03.068Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-11T05:38:22.806Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-07-18T01:52:51.563Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-08-16T15:03:59.605Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-09-27T01:36:28.259Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2018-10-12T02:06:08.531Z modifyDatastreamByValue MD_DESCRIPTIVE cdrApp 2019-03-20T20:23:37.148Z James Shellhammer Author Department of Pharmacology School of Medicine COORDINATION OF G PROTEIN AND MITOGEN-ACTIVATED PROTEIN KINASE SIGNALING PATHWAYS BY BRANCHED-CHAIN AMINO ACID METABOLITE SECOND MESSENGERS DURING OSMOTIC STRESS Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. Spring 2017 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text James Shellhammer Author Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. Spring 2017 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. Spring 2017 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. Spring 2017 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017-05 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid; G protein; metabolomics; mitogen-activated protein kinase; second messenger; signal transduction eng Doctor of Philosophy Dissertation Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 University of North Carolina at Chapel Hill Degree granting institution James Shellhammer Creator Department of Pharmacology School of Medicine Coordination of G Protein and Mitogen-Activated Protein Kinase Signaling Pathways by Branched-Chain Amino Acid Metabolite Second Messengers during Osmotic Stress Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid, G protein, metabolomics, mitogen-activated protein kinase, second messenger, signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Pharmacology Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 James Shellhammer Creator Department of Pharmacology School of Medicine Cells experience a variety of environmental signals, often simultaneously. These signals may encode opposing effects, so the response must be coordinated in a manner that promotes cell and organismal well-being. The expression of surface receptors, such as G protein-coupled receptors (GPCRs), aids in the detection of bioactive molecules. Once perceived by the cell, the signal is transduced to intracellular signaling components that carry out the appropriate response. Mitogen-activated protein kinase (MAPK) cascades are commonly activated in response to external stimuli that range from growth factors to environmental stresses. The budding yeast S. cerevisiae employs MAPK pathways to respond to mating pheromones and environmental stresses. The pheromone response pathway is a MAPK pathway regulated by a GPCR, and the high osmolarity glycerol (HOG) pathway is a parallel MAPK pathway that shares some components with the pheromone response pathway. Signal fidelity is maintained during simultaneous activation of these and other MAPK pathways through mechanisms including signal strength and duration, feedback regulation, and cross-pathway inhibition. In this dissertation, I identify a new means by which parallel MAPK pathways are regulated. I show that activation of the HOG pathway promotes the production of second messenger molecules derived from branched-chain amino acids. These new second messengers promote phosphorylation of the Gα subunit regulating the pheromone response pathway, and lead to reduced downstream transcriptional output. I also compare conventional and recently developed methods for analyzing MAPK activation and gene transcription. This work adds to our understanding of how signaling pathway cross-talk can maintain signal fidelity, and provides an update on the methods that can be used to best study these pathways for future discoveries. 2017 Biochemistry Pharmacology Molecular biology branched-chain amino acid; G protein; metabolomics; mitogen-activated protein kinase; second messenger; signal transduction eng Doctor of Philosophy Dissertation University of North Carolina at Chapel Hill Graduate School Degree granting institution Henrik Dohlman Thesis advisor Lee Graves Thesis advisor Robert Nicholas Thesis advisor Jay Brenman Thesis advisor Michael Emanuele Thesis advisor text 2017-05 Shellhammer_unc_0153D_16838.pdf uuid:ca27e8c3-4b7f-44dc-9433-714cec24aa4c 2019-07-05T00:00:00 2017-04-12T15:25:16Z proquest application/pdf 4308403 yes