Date of Award


Degree Type


Degree Name

Master of Science




Dr. Macarena Pampillo

Second Advisor

Dr. Moshmi Bhattacharya


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.



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