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Permanent link (DOI): https://doi.org/10.7939/R3XG9FK4D

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Regulation of Dab1 Splicing and Phosphorylation in Developing Neuronal Cells Open Access

Descriptions

Other title
Subject/Keyword
Dab1
Shp-2
Nova1
Splicing
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Dutta,Indrani
Supervisor and department
Dr. Roseline Godbout, Department of Oncology
Examining committee member and department
Dr. Gordon Chan, Department of Oncology
Dr. Mary Hitt, Department of Oncology
Dr. Yangxin Fu, Department of Oncology
Department
Department of Oncology
Specialization
Experimental Oncology
Date accepted
2013-12-23T14:05:32Z
Graduation date
2014-06
Degree
Master of Science
Degree level
Master's
Abstract
The Reelin signaling pathway is involved in the migration of neurons during brain development. Reelin binding to the receptors VLDLR (Very Low Density Lipoprotein Receptor) and ApoER2 (Apolipoprotein E Receptor 2) leads to Dab1 phosphorylation, thereby activating a cascade of downstream pathways. Here, we show that the neuronal splicing factor Nova1 is involved in the exclusion of Dab1 exons 9b and 9c. In particular, the expression of Nova1 isoform 2 (without its penultimate exon 4), coincides with exclusion of Dab1 exons 9b and 9c in a neuronal P19 cells. Nova1 knockdown in P19 cells results in increased inclusion of Dab1 exons 9b and 9c. We also show that Dab1 phosphorylation is regulated by the Shp-2 phosphatase. Intriguingly, in addition to its role as a phosphatase, Shp-2 can function as an adapter protein to recruit kinases that phosphorylate Dab1 in P19 cells but not HEK293T cells. These results suggest an additional level of complexity to the regulation of Dab1 phosphorylation during neuronal development.
Language
English
DOI
doi:10.7939/R3XG9FK4D
Rights
Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission.
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2014-06-15T07:12:36.590+00:00
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File format: pdf (Portable Document Format)
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File size: 3821316
Last modified: 2015:10:12 17:02:29-06:00
Filename: Dutta_Indrani_Spring 2014.pdf
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File title: Chapter 1:
File author: Indrani Dutta
Page count: 133
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