Hinkle Lab
Patricia M. Hinkle, Ph.D.
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Research Overview
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.
Recent Publications
Liang L, Sebag JA, Eagelston L, Serasinghe MN, Veo K, Reinick C, Angleson J,
Hinkle PM, and Dores RM. (2011) Functional expression of frog and rainbow trout melanocortin
2 receptors using heterologous MRAP1s. Gen. Comp. Endocrinol. 174:5-14.
Hinkle PM, Serasinghe MN, Jakabowski A, Sebag JA, Wilson KR, Haskell-Luevano C. (2001) Use of chimeric melanocortin-2 and -4 receptors to identify regions responsible for ligand specificity and dependence on melanocortin 2 receptor accessory protein. Eur. J. Pharmacol. 660:94-102.
Sebag JA and Hinkle PM. (2010) Regulation of G protein-coupled receptor signaling: specific dominant-negative effects of melanocortin 2 receptor accessory protein 2. Sci. Signal 3:ra28.
Gehret AU and Hinkle PM. (2010) Importance of regions outside the cytoplasmic tail of G-protein-coupled receptors for phosphorylation and dephosphorylation. Biochem J. 428:235-245.
Gehret AU, Jones BW, Tran PN, Cook LB, Greuber EK, Hinkle PM. (2010) Role of helix 8 of the thyrotropin-releasing hormone receptor in phosphorylation by G protein-coupled receptor kinase. Mol. Pharmacol. 77:288-297.
Contact Us
Patricia M. Hinkle, Ph.D.
University of Rochester
School of Medicine and Dentistry
Box 711
601 Elmwood Avenue
Rochester, NY 14642
Telephone: 585-275-4933
Fax: 585-273-2652
