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The role of Phosphoinositide 3-Kinase in the Regulation of Cardiac Morphology and Function

  • Author / Creator
    Guo, Danny
  • The traditional PI3K pathway relies on agonist mediated stimulation of PI3Kα through RTKs and PI3Kγ through GPCRs, which stimulate downstream enzymes such as Akt. This pathway has been found to be important in cardiomyocytes and cardiofibroblasts for regulating cardiac morphology and function. However, evidence has suggested that this traditional pathway does not fully represent the PI3K signaling cascade. We demonstrated that PI3Kγ regulates calcium through kinase independent interactions. PI3KγKO hearts rapidly develop systolic dysfunction and dilated cardiomyopathy in response to pressure overload due to excess matrix metalloproteinase mediated degradation of N-cadherin adhesion complexes. We also show a connection between the PI3K/PTEN and Casein Kinase 2, an enzyme that deactivates PTEN. Finally, our results demonstrate crosstalk between GPCRs and PI3Kα via transactivation of growth factor receptors. Our results provide insight into the regulation and the complexity of the PI3K/PTEN pathway.

  • Subjects / Keywords
  • Graduation date
    2011-06
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/R3DK8G
  • 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
    English
  • Institution
    University of Alberta
  • Degree level
    Master's
  • Department
    • Medicine
  • Supervisor / co-supervisor and their department(s)
    • Gary D. Lopaschuk (Pharmacology and Pediatrics)
    • Gavin Y. Oudit (Medicine)
  • Examining committee members and their departments
    • Jason R.B. Dyck (Pediatrics)
    • Allan Murray (Medicine)
    • Joseph Casey (Physiology)