Molecular cloning of neural receptor-like protein tyrosine phosphatase zeta/beta and regulation of itsmRNA expression during development and following sciatic nerve injury.
Item
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Title
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Molecular cloning of neural receptor-like protein tyrosine phosphatase zeta/beta and regulation of itsmRNA expression during development and following sciatic nerve injury.
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Identifier
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AAI9807957
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identifier
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9807957
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Creator
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Li, Ji.
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Contributor
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Adviser: Stephen R. J. Salton
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Date
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1997
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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, Neuroscience | Biology, Molecular
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Abstract
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Protein tyrosine phosphorylation is recognized as one of the main eukaryotic cell signaling mechanisms. The overall level of cellular protein tyrosine phosphorylation is determined by the dynamic balance between the competing actions of protein tyrosine kinases and protein tyrosine phosphatases (PTPs). Identification of a number of neurotrophin receptors as receptor tyrosine kinases has emphasized the integral role that tyrosine phosphorylation is likely to play within the nervous system. To identify PTP genes that regulate tyrosine phosphorylation during development and regeneration of the nervous system, this thesis describes the molecular cloning of the rat neural receptor-like protein tyrosine phosphatase (RPTP) RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar}, the molecular mechanisms responsible for generating various isoforms of RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar}, and the regulation of expression of various RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} mRNAs during neural development and following peripheral nerve injury.;I have isolated overlapping rat RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} cDNA clones. Analysis indicates that the RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} coding sequence has been highly conserved during mammalian evolution.;I have determined that three major RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} transcripts are generated through alternative mRNA splicing and transcribed from the same gene. These three transcripts are co-expressed extensively in the developing and mature CNS and PNS. I have also characterized additional RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} isoforms that differ in the juxtamembrane region, suggests that regulation of RPTP dimerization may control enzymatic activity of the phosphatase.;Lastly, I have demonstrated that RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} mRNAs are greatly induced in distal segments of sciatic nerve following crush lesions. The time course of this induction correlates well with the response of Schwann cells to injury in this paradigm. Furthermore, I found a significant difference in the relative abundance of RPTP{dollar}\zeta{dollar}/{dollar}\beta{dollar} isoforms expressed in the PNS and CNS. The short transcript, which has been shown to be able to induce neurite outgrowth and promote neuronal differentiation, is most abundant in the PNS, whereas the phosphacan transcript, which is often being associated with inhibition of neuronal adhesion and neurite outgrowth, is most abundant in the CNS. These differences could account in part for the strikingly different regeneration capabilities of the PNS and CNS.
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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.
