GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p G alpha subunit and regulates cell growth in parallel to RAS genes.
Item
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Title
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GPR1 encodes a putative G protein-coupled receptor that associates with the Gpa2p G alpha subunit and regulates cell growth in parallel to RAS genes.
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Identifier
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AAI9924855
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identifier
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9924855
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Creator
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Xue, Yong.
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Contributor
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Adviser: Jeanne Hirsch
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Date
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1999
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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, Microbiology
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Abstract
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The studies described here aim to understand the function of GPA2, which encodes a heterotrimeric G protein alpha subunit in Saccharomyces cerevisiae. The gene was cloned based on its homology to mammalian G alpha subunit genes, but had no demonstrated functions other than that GPA2 might be involved in the Ras/cAMP pathway in Saccharomyces cerevisiae (60). In my thesis studies, Gpa2p was shown to be localized to the plasma membrane. A gpa2 disruption was found to cause synthetic lethality with a ras2 disruption, and overexpression of Gpa2p or a constitutively active allele of GPA2 showed similar physiological effects as activation of the Ras/cAMP pathway. Further studies also suggested that GPA2 signaling is independent of RAS genes.;In a two-hybrid screen, GPR1 was isolated as an interacting protein for GPA2. GPR1 is a previously uncharacterized open reading frame. It shows limited sequence homology to members of the G-protein coupled receptor (GPCR) family and also has seven transmembrane domains characteristic of this receptor family. Further genetic studies confirmed that GPA2 signals downstream of GPR1 in the same pathway. A Gpr1p-GFP fusion protein was also localized to the plasma membrane of yeast. Based on these findings and other evidence, we therefore propose that GPR1 is a novel G protein coupled receptor for GPA2.;Based on the expression pattern of GPR1 and the role of GPA2 and GPR1 in pseudohyphal differentiation, we also propose that the main function of the GPR1/ GPA2 pathway is to sense the availability of nutrients, especially nitrogen sources, and to initiate appropriate cellular response. This growth regulation function of GPA2 acts independently of the yeast RAS genes which have well established roles in nutrient signaling. Finally, I have also obtained preliminary evidence suggesting that GPR1 may have GPA2 independent signaling functions.
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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.
