Generation of temperature-sensitive mutants ofv-Ros, oncogenic insulin and insulin-like growth factor-I receptors and identification of the insulin receptor interacting proteins.
Item
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Title
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Generation of temperature-sensitive mutants ofv-Ros, oncogenic insulin and insulin-like growth factor-I receptors and identification of the insulin receptor interacting proteins.
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Identifier
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AAI9720078
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identifier
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9720078
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Creator
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Chen, Jing.
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Contributor
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Adviser: Lu-Hai Wang
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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
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Abstract
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Receptor protein tyrosine kinases (RPTKs) are a family of transmembrane proteins with intrinsic tyrosine kinase activity. They play important roles in many cellular events including cell growth, metabolism and differentiation. My Ph.D. thesis work focuses on insulin receptor (IR), insulin-like growth factor I receptor (IGFR) and oncogene v-ros, all of which belong to a subfamily of RPTKs.;Oncogene v-ros, carried by avian sarcoma virus UR2, encodes a p68 gag-ros transforming protein with intrinsic tyrosine kinase activity. Temperature sensitive mutants of UR2 have been isolated in 1985. In this thesis, the molecular basis for ts251, a temperature sensitive (ts) mutant of UR2, has been identified. A point mutation in the catalytic loop of the kinase domain of UR2 is responsible for the ts phenotype and properties of ts251. The significance of the mutation is further demonstrated by introducing the same mutation into gag-IR and gag-IGFR receptor PTKs and obtaining a similar ts phenotype and properties of these receptor PTKs as well.;The second aspect of this thesis is the identification of Stat5, as a potential physiological substrate of insulin receptor. Insulin receptor is very important in many biological functions including regulation of glucose homeostasis, stimulation of the uptake of amino acids, regulation of gene expression and promotion of cell proliferation and differentiation. Using yeast two hybrid system, C-terminal portion of human Stat5b (Stat5b-Ct) has been identified to interact with IR. Stat5b-Ct can be tyrosine phosphorylated in vitro and in vivo by IR. Furthermore, Stat5 is tyrosine phosphorylated and activated in insulin perfused livers and in fasted-and-refed mice. Taken together, Stat5 could be a potential physiological substrate of IR.
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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.
