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

  • Author / Creator
    McTague, James R
  • 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.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Department of Physiology
  • Specialization
    • Endocrinology
  • Supervisor / co-supervisor and their department(s)
    • Dr. Ho, Anthony (Department of Physiology)
  • Examining committee members and their departments
    • Dr. Karpinski, Edward (Department of Physiology)
    • Dr. Morrish, Donald (Department of Medicine)
    • Dr. Ho, Anthony (Department of Physiology)
    • Dr. Kline, Loren (Deparment of Physiology