Phospholipid metabolism activated byv-Src.
Item
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Title
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Phospholipid metabolism activated byv-Src.
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Identifier
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AAI9325151
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identifier
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9325151
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Creator
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Song, Jian-guo.
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Contributor
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Adviser: David A. Foster
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Date
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1993
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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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Chemistry, Biochemistry | Biology, Cell | Biology, Molecular
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Abstract
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Activation of the protein-tyrosine kinase of v-Src in BALB/c 3T3 cells results in the rapid increase in diglycerides (DG), which function as intracellular second messengers. DG is the physiological activator of protein kinase C (PKC). By differential radiolabeling of phospholipids, the major source for the increased DG level in response to v-Src activation was identified as phosphatidylcholine (PC). Increased generation of intracellular choline and phosphatidic acid (PA) in response to v-Src was also observed. Consistent with the above data which suggest the involvement of a phospholipase D (PLD)-mediated PC hydrolysis, v-Src also increased intracellular transphosphatidylation activity, which is characteristic of PLD activity. Thus, the v-Src-induced increase in DG most likely results from the activation of a PLD which generates PA, followed by the hydrolysis of PA to DG by a PA phosphatase.;Phorbol esters that activate protein kinase C (PKC), markedly increase PLD activity in BALB/c 3T3 cells. v-Src- and phorbol ester-induced PLD activities were differentially sensitive to inhibitors of PKC and depleting cells of PKC. Neither depleting cells of PKC nor treatment with the PKC inhibitor staurosporine inhibited v-Src-induced PLD activity; whereas, both PKC-depletion and staurosporine treatment inhibited TPA-induced PLD activity. Additional differences between the increased PLD activity in v-Src transformed cells and the PLD activity induced by phorbol esters were established using a differential radiolabeling strategy. These data demonstrate that v-Src activates a PLD activity that is independent of PKC. Thus, it is likely that the DG generated by the combined action of PC-PLD and PA phosphatase are responsible for the activation of PKC by v-Src.;Taken together, this data suggest that v-Src activates a distinct PLD activity that is specific for PC. The potential for the generating multiple intracellular signals through complete phospholipid metabolism is described.
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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.
