All ETDs from UAB

Advisory Committee Chair

Stuart J Frank

Advisory Committee Members

David A Schneider

Kurt R Zinn

Martin E Young

Thomas M Ryan

Document Type


Date of Award


Degree Name by School

Doctor of Philosophy (PhD) Heersink School of Medicine


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.



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