Characterization of the effect of protein phosphatase 2A uponv-Src-induced cell signaling.
Item
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Title
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Characterization of the effect of protein phosphatase 2A uponv-Src-induced cell signaling.
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Identifier
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AAI9417468
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identifier
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9417468
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Creator
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Gupta, Ruchika W.
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Contributor
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Adviser: David A. Foster
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Date
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1994
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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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Constitutive activity of the v-Src protein-tyrosine kinase results in cell transformation and initiates multiple intracellular signalling mechanisms. Okadaic acid (OA) is an inhibitor of the serine/threonine protein phosphatases 1 and 2A (PP1 and PP2A). Addition of OA to v-Src-transformed BALB/c 3T3 cells reverted them to a flat morphology, increased fibronectin levels in the extra-cellular matrix, reduced saturation density, and inhibited the formation of colonies in soft agar. The ability of v-Src-transformed cells to proliferate in low serum was also inhibited by okadaic acid. These data indicate that OA can inhibit v-Src-induced cell transformation. v-Src can activate promoters under the control of 12-o-tetradecanoylphorbol-13-acetate (TPA) response elements (TREs) and serum response elements (SREs). The induction of SRE-mediated gene expression by v-Src requires Ras and Raf-1, while the induction of TRE-mediated gene expression by v-Src requires Ras but is independent of Raf-1. The induction of TRE-mediated gene expression by v-Src and v-HaRas increased in the presence of the catalytic subunit of PP2A The induction of SRE-mediated gene expression by v-Src and v-HaRas, however, was inhibited by PP2A. PP2A had no effect upon v-Raf-induced SRE-mediated gene expression. These findings implicate serine/threonine phosphatases in v-Src-induced cell signalling. They further suggest that PP2A differentially regulates two intracellular signals activated by v-Src and v-HaRas, and that the effect of PP2A upon v-Src-and v-HaRas-induced SRE-mediated gene expression is upstream from Raf-1 activation. Thus, serine/threonine phosphatases may play an important role in the transformation of cells by v-Src; their activity may either inhibit or potentiate v-Src-induced cell signalling depending upon the effect of dephosphorylation on the activity of the substrate protein.
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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.
