Date of Award


Degree Type


Degree Name

Master of Science


Pharmacology and Toxicology


Dr. Moshmi Bhattacharya

Second Advisor

Dr. Lina Dagnino

Third Advisor

Dr. Frank Beier


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.



To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.