Patricia M. Hinkle, Ph.D.
We are interested in the broad question of how a hormone triggers a characteristic set of cellular responses. We use a number of model systems (pituitary cells, cell lines, transgenic animals) to study signal pathways for a hypothalamic peptide hormone, TRH, which acts via a G protein coupled receptor to increase cytoplasmic calcium and protein kinase C activity. Modern technologies allow us to study hormonal responses in live cells. For example, we can "tag" signaling proteins with green fluorescent protein (GFP) and then follow their movements in the cell during hormonal stimulation in real time. We monitor intracellular calcium in the cytoplasm and the endoplasmic reticulum using several fluorescence imaging techniques. In addition, we use biochemical and genetic approaches to identify proteins that interact with the receptor during biosynthesis, signaling and desensitization. Similar strategies are being used to ask how insulin secretion by the pancreatic beta cell is controlled. The long-term goal is to understand signal transduction in endocrine cells at a molecular and cellular level.
The movie shows the movement of GFP-beta-arrestin after TRH addition. When TRH binds to its receptor, the receptor changes conformation, activates Gq, and becomes phosphorylated by specific receptor kinases; the phospho-receptor binds to beta-arrestin. The movie covers about 10 min.
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