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Permanent link (DOI): https://doi.org/10.7939/R3S937

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Regulation of Transducer of Regulated CREB 1 (TORC1) in the Rat Pineal Gland Open Access

Descriptions

Other title
Subject/Keyword
TORC
CRTC1
TORC1
CRTC
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
McTague, James R
Supervisor and department
Dr. Ho, Anthony (Department of Physiology)
Examining committee member and department
Dr. Kline, Loren (Deparment of Physiology
Dr. Ho, Anthony (Department of Physiology)
Dr. Morrish, Donald (Department of Medicine)
Dr. Karpinski, Edward (Department of Physiology)
Department
Department of Physiology
Specialization
Endocrinology
Date accepted
2012-07-20T14:18:45Z
Graduation date
2012-11
Degree
Master of Science
Degree level
Master's
Abstract
The transducers of regulated cAMP-response element-binding protein (CREB)(TORC) are a family of co-activators that can enhance CREB-mediated gene transcription. Existing literature remains elusive of a detailed regulatory mechanism for specific TORC isoforms, and suggests dephosphorylation and nuclear accumulation are mediated through the same signalling pathways for all isoforms. Through the use of immunoblot analysis and nuclear/cytosolic fractionation we examined the norepinephrine stimulated signalling mechanism that mediates the dephosphorylation and nuclear accumulation of TORC1 in the rat pineal gland. This study reveals that the dephosphorylation and subsequent nuclear accumulation of TORC1 leading to its activation, is regulated through the α1-adrenergic receptor causing an elevation of intracellular Ca2+ and the activation of protein phosphatase 2B. Once in the nucleus, TORC1 requires constant α1- and β-adrenergic receptor activation to maintain the dephosphorylation and nuclear retention. Furthermore, we demonstrate that salt-inducible kinase 1 (SIK1) is not responsible for regulating the cellular distribution of TORC1.
Language
English
DOI
doi:10.7939/R3S937
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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