Date of Award

2009

Degree Type

Thesis

Degree Name

Master of Science

Program

Physiology

Supervisor

Dr. Macarena Pampillo

Second Advisor

Dr. Moshmi Bhattacharya

Abstract

The neuropeptide kisspeptin and its cognate receptor, G protein-coupled receptor 54 (GPR54) are important regulators of the hypothalamic-pituitary-gonadal axis. Recent research has demonstrated that GPR54 undergoes agonist-dependent desensitization, but underlying molecular mechanisms were unknown. My study reports for the first time on the role of G protein-coupled receptor kinase 2 (GRK2) and (3-arrestin in regulating GPR54 signaling in HEK 293 and MDA MB-231 cells. My study reveals that GRK2 mediates the desensitization of GPR54 in HEK 293 cells and that b-arrestin 2 is required for GPR54 signaling to ERK1/2 in MDA MB-231 cells. The significance of these novel findings in developing molecular-based therapies for treating certain cancers and endocrine-related disorders is discussed.

Share

COinS
 
 

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.