Date of Award
2008
Degree Type
Thesis
Degree Name
Master of Science
Program
Pharmacology and Toxicology
Supervisor
Dr. Moshmi Bhattacharya
Second Advisor
Dr. Lina Dagnino
Third Advisor
Dr. Frank Beier
Abstract
Lysophosphatidic Acid (LPA) is a major constituent of serum and is involved in a variety of physiological and pathophysiological processes. LPA signals via the G-protein coupled receptors (GPCRs), LPA1-7, where LPAi and LP A2 receptors are ubiquitously expressed. The molecular mechanisms of desensitization and endocytosis involved in the regulation of LPA signaling by those two receptors are unknown and are the focus of this study. We show that the small GTPase RalA and the enzyme phospholipase D2 do not play a role in the endocytosis of LPAi and LPA2 receptors in human embryonic kidney (HEK 293) cells. In contrast, we demonstrate that RalA is involved in mediating LPAi receptor signaling. Furthermore, we identified a novel interaction between RalA and GRK2 in response to LPAi receptor stimulation. Our findings also indicate that these two proteins appear to compete for binding to LPAi receptors. Therefore we identified Ral as a novel binding partner of GRK2 and this could be a potential therapeutic target for the various pathophysiological processes initiated by LPA signaling.
Recommended Citation
Aziziveh, Adel, "THE MOLECULAR MECHANISMS OF DESENSITIZATION AND ENDOCYTOSIS OF LPA1 AND LPA2 RECEPTORS" (2008). Digitized Theses. 4379.
https://ir.lib.uwo.ca/digitizedtheses/4379