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Permanent link (DOI): https://doi.org/10.7939/R3DK8G

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

Descriptions

Other title
Subject/Keyword
Heart
Cell Signaling
PI3K
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Guo, Danny
Supervisor and department
Gary D. Lopaschuk (Pharmacology and Pediatrics)
Gavin Y. Oudit (Medicine)
Examining committee member and department
Jason R.B. Dyck (Pediatrics)
Joseph Casey (Physiology)
Allan Murray (Medicine)
Department
Medicine
Specialization

Date accepted
2011-04-15T18:16:23Z
Graduation date
2011-06
Degree
Master of Science
Degree level
Master's
Abstract
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.
Language
English
DOI
doi:10.7939/R3DK8G
Rights
License granted by Danny Guo (dguo1@ualberta.ca) on 2011-04-15T16:48:03Z (GMT): 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 the above terms. The author reserves all other publication and other rights in association with the copyright in the thesis, and except as herein 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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