Advisory Committee Chair
Stuart J Frank
Advisory Committee Members
David A Schneider
Kurt R Zinn
Martin E Young
Thomas M Ryan
Document Type
Dissertation
Date of Award
2016
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Growth hormone receptor (GHR) and prolactin receptor (PRLR) are transmembrane glycoproteins cytokine receptors that are structurally homologous. Each can pre-homodimerize and ligand binding of each activates JAK2-STAT signaling pathways by inducing conformational change within the receptor homodimer. Human GHR can be activated by growth hormone (GH) while human PRLR can be activated by both GH and prolactin (PRL). We devised a split luciferase complementation assay, in which one receptor is fused to the N-terminal fragment of luciferase and the other receptor is fused to the C-terminal fragment of luciferase. When the two receptors approximate, luciferase activity (complementation) results. Using this assay, we reported ligand-independent GHR-GHR complementation and a GH-induced complementation change characterized by an acute augmentation above basal signal. We found a similar basal complementation of PRLR-PRLR and that ligand (both GH and PRL) induced augmentation of complementation. For GHR-PRLR, ligand-independent complementation was also detected; however, treatment with either GH or PRL caused a decline in complementation, distinct from the GHR-GHR or PRLR-PRLR situations. Based on these and other antagonists-based data, we proposed a model in which GHR and PRLR associate as a heteromer composed of GHR homodimers and PRLR homodimers rather than as GHR-PRLR heterodimers.
Recommended Citation
Liu, Ying, "Development Of A Split Luciferase Complementation Assay To Investigate Growth Hormone Receptor/ Prolactin Receptor Homo-/ Hetero-Association" (2016). All ETDs from UAB. 2314.
https://digitalcommons.library.uab.edu/etd-collection/2314
