Intracellular signals activated by the Src oncoprotein.
Item
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Title
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Intracellular signals activated by the Src oncoprotein.
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Identifier
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AAI9720083
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identifier
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9720083
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Creator
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Curto, Marcello.
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Contributor
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Adviser: David A. Foster
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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 | Health Sciences, Oncology
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Abstract
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How the oncogenic tyrosine kinase v-Src causes the uncontrolled cell division typical of neoplastic cells, is still unclear. The expression of immediate early genes (IEGs) is induced by several mitogenic stimuli as well as by v-Src, suggesting that increased expression of these mitogen-responsive genes might contribute to v-Src-induced cellular transformation. Multiple intracellular signals mediate v-Src-dependent induction of IEGs, but the molecular mechanisms governing their activation are currently unknown. Here we have investigated the possibility that specific regions of the Src protein, are required to control different sets of intracellular signals leading to transcriptional activation of IEGs. To accomplish this, several Src genes, mutated at regions involved in the regulation of intracellular signals, were tested for the ability to induce transcriptional activation of different promoter elements that regulate IEG expression. During the course of these experiments, we found that while transiently transfected Src-genes could induce strong activation of all the promoter element tested, these were poorly or not activated in cells chronically transformed by v-Src, suggesting that an increased expression of IEGs might not be necessary for determining a transformed phenotype. Therefore, we sought to identify other intracellular signals that may account for the induction of a proliferative phenotype by v-Src. In a different set of experiments, we found that two distinct receptors for the mitogens FGF and PDGF, are constitutively phosphorylated on tyrosine, and complexed with signal transducing molecules such as Grb2, Sos and PI3K. Since similar molecular events are induced upon stimulation with physiological mitogens, these experiments suggest that a v-Src-dependent intracellular activation of various growth factor receptors may result in the generation of unregulated mitogenic signals, ultimately leading to cellular transformation.
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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.
