Identification and characterization of two glucose sensing/signaling pathways stimulating glucose-induced inactivation of maltose permease in Saccharomyces.
Item
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Title
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Identification and characterization of two glucose sensing/signaling pathways stimulating glucose-induced inactivation of maltose permease in Saccharomyces.
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Identifier
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AAI9807947
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identifier
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9807947
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Creator
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Jiang, Hua.
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Contributor
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Adviser: Corinne A. Michels
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Date
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1997
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular | Biology, Genetics | Biology, Cell
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Abstract
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Addition of glucose to maltose fermenting Saccharomyces cerevisiae cells causes a rapid and irreversible loss of maltose transport activity, resulting both from the repression of transcription of the maltose permease and from post-translational inactivation of maltose permease, which is referred to as glucose-induced inactivation of maltose permease. The inactivation process consists of two components: inhibition of maltose uptake, and proteolysis of maltose permease. The latter is dependent on endocytosis and vacuolar proteases, and is not dependent on the proteosome.;RGT2, GRR1 and RGT1 are involved in glucose sensing and signal transduction pathways regulating gene expression. By using deletion and dominant point mutations in these genes, two glucose sensing/signaling pathways stimulating glucose-induced inactivation were identified and further investigation of each pathway was carried out.;Pathway 1 is predominantly responsible for the proteolysis of maltose permease. It is independent of glucose transport and uses a putative high-affinity glucose transporter, Rgt2p, as the sensor for high levels of extracellular glucose. The downstream components of this pathway include Grr1p and Reg1p. Loss of Grr1p appears to block the activity of Reg1p possibly by stimulating Reg1p degradation.;Pathway 2 stimulates both the proteolysis of maltose permease and the rapid inhibition of maltose uptake. By using a series of sugar kinase mutations, I provide evidence that the initial steps of sugar metabolism, including transport and phosphorylation, are required for generating the inactivation signal. Any of the three hexokinases (hexokinase 1, 2 and glucokinase) is capable of serving as a sensor for intracellular glucose. Grr1p is indirectly involved in Pathway 2 because it is required for expression of high-affinity glucose transporters, encoded by the HXT genes. A number of other fermentable carbon sources, including fructose, mannose, galactose, and maltose, and the nonmetabolized glucose analog 2-deoxy-glucose also can stimulate inactivation of maltose permease to different extent through Pathway 2.;In conclusion, Pathway 1 and Pathway 2 are two distinct but interconnected pathways monitoring extracellular and intracellular glucose levels and transducing inactivation signals to different downstream components. These two pathways together with other known glucose signal transduction pathways ensure the rapid transition from utilization of alternative carbon sources to glucose fermentation by controlling gene expression and protein stability.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
