Characterization of paxillin, Phospholipase D and their functional interaction
Item
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Title
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Characterization of paxillin, Phospholipase D and their functional interaction
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Identifier
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d_2009_2013:65402b41d3ca:11379
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identifier
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11777
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Creator
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Pribic, Jelena,
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Contributor
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Derrick Brazill
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Date
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2012
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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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Biochemistry | Breast cancer | Erk | Metastasis | Paxillin | Phospholipase D
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Abstract
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The actin cytoskeleton plays a fundamental role in various processes including differentiation, migration, endocytosis and exocytosis. An adapter protein, paxillin, as well as an enzyme, Phospholipase D (PLD), have been associated with processes based on actin cytoskeleton regulation. Such regulation is critical for the development of Dictyostelium discoideum. To gain better insight into the roles of paxillin and PLD and to investigate their potential interactions, we study the paxillin and PLD orthologs, PaxB and PldB, respectively. Previous work showed that in Dictyostelium discoideum, paxillin (PaxB) and Phospholipase D (PldB) colocalize and co-immunoprecipitate, suggesting that they physically interact. We found that the phenotypes observed during development, cell sorting and several actin-required processes including cAMP chemotaxis, cell-substrate adhesion, actin polymerization, phagocytosis, and exocytosis reveal a genetic interaction between paxB and pldB suggesting a functional interaction between gene products. Taken together, our data point to PldB being a required binding partner of PaxB during processes involving actin reorganization.;Based on our study in the model organism Dictyostelium discoideum , we examined whether a similar relationship between paxillin and PLD exists in the highly aggressive human breast cancer cell line MDA-MB-231. We investigated the role of PLD activity on paxillin regulation, Erk activation and formation of a paxillin-Erk and paxillin-FAK complex. Inhibition of PLD activity led to an increase in paxillin tyrosine phosphorylation, a decrease in Erk activation, and enhanced association of paxillin with Erk. In addition, we found that paxillin tyrosine phosphorylation depends upon Erk activity and may be a consequence of an increased association with FAK. Taken together, our results suggest that Erk activity is governed by PLD activity and regulates the tyrosine phosphorylation of paxillin, potentially explaining its role in cell motility. This study indicated that PLD, paxillin, FAK and Erk participate in the same signaling pathway in this breast cancer cell line. The proposed studies will allow further insight into the role of these proteins in cancer and better understanding of the clinical course of disease.
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Type
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dissertation
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Source
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2009_2013.csv
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degree
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Ph.D.
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Program
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Biochemistry
