Characterization of intracellular intermediates inv-Fps-initiated signal transduction.
Item
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Title
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Characterization of intracellular intermediates inv-Fps-initiated signal transduction.
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Identifier
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AAI9224788
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identifier
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9224788
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Creator
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Alexandropoulos, Konstantina.
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Contributor
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Adviser: David A. Foster
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Date
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1992
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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, Cell
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Abstract
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Fujinami Sarcoma Virus (FSV), encodes a phosphoprotein, v-Fps with a kinase activity that phosphorylates proteins on tyrosine residues. The protein tyrosine kinase (PTK) activity of v-Fps can cause rapid transformation in vitro and tumor formation in vivo. Activating the PTK activity of v-Fps leads to induction of intracellular signaling pathways through the activation of cytoplasmic signaling molecules. In this study, induction of gene expression through activation of the PTK activity of a temperature sensitive (ts) derivative v-Fps was utilized in order to study v-Fps-induced signaling. Inhibitors, specific for putative signaling molecules, that interfere with induction of transcription were used to implicate these molecules in v-Fps initiated signal transduction. Evidence is presented that v-Fps activates a PKC-dependent pathway mediated through a GTP-binding protein (G-protein). Involvement of a heterotrimeric G-protein was suggested using nonhydrolyzable GTP and GDP analogs. GTP{dollar}\tau{dollar}S induced the expression of a v-Fps responsive reporter gene, and phosphorylation of a PKC substrate. GDP{dollar}\beta{dollar}S blocked induction of both of these phenotypes in response to v-Fps but not in response to phorbol esters. These data are consistent with involvement of a G-Protein functioning upstream of PKC in v-Fps signaling. v-Fps also induces expression of a reporter gene in a PKC-independent manner. Dominant negative inhibitors of c-HaRas and Raf-1 inhibit PKC-independent signals induced by v-Fps, where Ras functions upstream of Raf-1. The dominant inhibitor of Ras also inhibits PKC-mediated signals, and depletion of PKC shows that Ras functions downstream from PKC.;The data presented here suggest that v-Fps can activate at least two distinguishable intracellular signaling pathways, one mediated by a heterotrimeric G-protein and PKC, and one that is sequentially dependent upon Ras and Raf-1 and is PKC-independent. The data also suggest that Ras plays a central role as a transducing molecule in v-Fps-induced signaling, by mediating two distinct intracellular signaling pathways.
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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.
