The involvement of Ras and Ral GTPases in v-Src-induced intracellular phospholipid signalling.
Item
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Title
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The involvement of Ras and Ral GTPases in v-Src-induced intracellular phospholipid signalling.
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Identifier
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AAI9605607
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identifier
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9605607
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Creator
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Jiang, Hong.
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Contributor
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Adviser: David A. Foster
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Date
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1995
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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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Tyrosine kinase v-Src-induced activation of phospholipase D (PLD), which leads to the generation of phospholipid second messengers, is GTP binding protein (G-protein)-dependent. Two G-proteins, Ras and Ral, have been found to mediate PLD activity. The involvement of Ras was supported by the finding that a neutralizing antibody to Ras was able to block membrane PLD activity, and GTP bound Ras was able to interact with a factor(s) that contributes to the activation of PLD. Ral, another Ras family G-protein, was identified as a Ras downstream effector required for the activation of PLD. First, the amino terminal domain of Ral was found to be associated with PLD. PLD activity was inhibited by a dominant inhibitory and a effector domain mutants of Ral expressed in v-Src-transformed NIH cells. Furthermore, overexpression of Ral protein enhanced PLD activity in v-Src-transformed, but not in parental NIH cells. A Ras/Ral GTPase cascade is proposed for v-Src-induced PLD activity. Ras is known to be activated by v-Src and interacts with RalGDS (Ral guanine nucleotide dissociation stimulator). This interaction localizes RalGDS to the membrane and activates Ral. Ral is then recruited and brings associated PLD to the Ras/RalGDS/Ral-PLD signalling complex where PLD become activated. In addition, Ral is found to be involved in cell transformation by oncogenic Src and Ras. Therefore, the activation of PLD mediated by Ras/Ral GTPase cascade might contribute to oncogenic Src- and Ras-induced cell 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.
