John Regan, PhD

Professor
Department(s): 
Pharmacology & Toxicology

G-protein coupled receptors (GPCR) are integral membrane proteins that transduce extracellular hormonal signals from the plasma membrane to the interior of the cell. This large family of receptors is related both structurally and functionally. Structurally, GPCRs share a characteristic "seven transmembrane motif" which means that there are seven regions of the receptor that cross the plasma membrane. Functionally, GPCRs share the ability to interact with so-called ‘G-proteins’ following stimulation of the receptor by a hormonal signal. The G-proteins, or "guanine nucleotide binding regulatory proteins," lend their name to the GPCRs, but they actually represent a separate family of proteins. Upon stimulation of a GPCR by a hormonal signal one or more G-proteins are activated; which in turn activate additional families of proteins, which activate more proteins, etc. The end result of this is an increasing complex signaling cascade that culminates in a macroscopic response; e.g., muscle contraction, nerve depolarization, shape change, etc. The general interests of the Regan laboratory are to understand how drugs work by studying the molecular biology and signal transduction mechanisms of the G-protein coupled receptors (GPCRs). There are hundreds of different GPCRs; the ones under investigation in the Regan lab include the adrenergic and prostaglandin receptors that mediate the actions of adrenaline (epinephrine) and the prostaglandins, respectively. To study the GPCRs and their signal transduction pathways a variety of recombinant DNA approaches are utilized including the polymerase chain reaction (PCR), gene cloning, heterologous expression, and site-directed mutagenesis. In addition, functional approaches are employed such as the biochemical determination of second messenger function (e.g., protein phosphorylation, cAMP, calcium signaling) as well as immunofluorescence microscopy and real-time videomicroscopy. The goal of this work is to contribute to a better understanding of the GPCRs, their role in the biology of the cell, and their potential as targets for drug development.

Education: 

BS, University of California, Berkeley, 1972, Zoology

MS, University of California, Berkeley, 1975, Nutritional Science

PhD, University of Arizona, 1981, Pharmacology & Toxicology

Honors & Awards

1996, Linköping University, Sweden M.D. honoris causa

1992, Syntex Prize in Receptor Pharmacology

Publications

Fujino H, S. Salvi, JW Regan. Differential regulation of phosphorylation of the cAMP response element-binding protein after activation of EP2 and EP4 prostanoid receptors by prostaglandin E2. Mol Pharmacol 68:251-259, 2005.

Fujino H, GA Vielhauer, JW Regan. Prostaglandin E2 selectively antagonizes prostaglandin F2a-stimulated T-cell factor/b-catenin signaling pathway by the FPB prostanoid receptor. J Biol Chem 279:43386-43391, 2004.

Fujino H, JW Regan. Prostaglandin F2a amplifies tumor necrosis factor-a promoter activity by the FPB prostanoid receptor. Biochem Biophys Res Comm 317:1114-1120, 2004.

Smith-Thomas L, M Moustafa, CS Spada, L Shi, RA Dawson, M Wagner, C Balafa, KM Kedzie, JW Reagan, AHP Krauss, DF Woodward, S MacNeil. An in vitro model to demonstrate latanoprost-induced pigmentation in human iridial melanocytes. Exp Eye Res 78:973-985, 2004.

Vielhauer GA, H Fujino, JW Regan. Cloning and localization of FPs, a six-transmembrane mRNA splice variant of the human FP prostanoid receptor. Arch Biochem Biophys 421:175-185, 2004.

Fujino H, Wei Xu, JW Regan. Prostaglandin E2 induced functional expression of early growth response factor-1 by EP4, but not EP2, prostanoid receptors via the phosphatidylinositol 3-kinase and extracellular signal-regulated kinases. J Biol Chem 278:12151-12156, 2003.

Fujino H, JW Regan. Prostaglandin F2a stimulation of cyclooxygenase-2 promoter activity by the FPB prostanoid receptor. Eur J Pharmacol 465:39-41, 2003.

Porter AC, SPS Svensson, WD Stamer, JJ Bahl, JG Richman, JW Regan. Alpha-2 adrenergic receptors stimulate actin organization in developing fetal rat cardiac myocytes. Life Sci 72:1455-1466, 2003.

Weber TJ, LM Markillie, WB Chrisler, GA Vielhauer, JW Regan. Modulation of clonal selection processes by the prostaglandin F2a receptor. Mol Carcinogenesis 35:163-172, 2002.

Fujino H, D Srinivasan, JW Regan. Cellular conditioning and activation of b-catenin signaling by the FPB prostanoid receptor. J Biol Chem 277:48786-48795, 2002.

Fujino H, KA West, JW Regan. Phosphorylation of glycogen synthase kinase-3 and stimulation of T-cell factor signaling following activation of EP2 and EP4 prostanoid receptors by prostaglandin E2. J Biol Chem 277:2614-2619, 2002.

Srinivasan D, H Fujino, JW Regan. Differential internalization of the prostaglandin F2a receptor isoforms: Role of protein kinase C and clathrin. J Pharmacol Exp Ther 302:219-224, 2002.

Anthony TL, H Fujino, KL Pierce, AJ Yool, JW Regan. Differential regulation of Ca2+-dependent Cl- currents by FP prostanoid receptor isoforms in Xenopus oocytes. Biochem Pharmacol 63:1797-1806, 2002.

Huang Y, WD Stamer, DV Kumar, PA St.John, JW Regan. Expression of a2-adrenergic receptor subtypes in prenatal rat spinal cord. Dev Brain Res 133:93-104, 2002.

Ostrom RS, C Gregorian, RM Drenan, Y Xiang, JW Regan, PA Insel. Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase. J Biol Chem 276:42063-42069, 2001.

Thompson EJ, A Gupta, GA Vielhauer, JW Regan, GT Bowden. The growth of malignant keratinocytes depends on signaling through the PGE2 receptor EP1. Neoplasia 3:402-410, 2001.

Fujino H, JW Regan. FP prostanoid receptor activation of a T-cell factor/b-catenin signaling pathway. J Biol Chem 276:12489-12492, 2001.

Fujino H, KL Pierce, D Srinivasan, CE Protzman, AH Krauss, DF Woodward, JW Regan. Delayed reversal of shape change in cells expressing FPB prostanoid receptors: Possible role of receptor resensitization. J Biol Chem 275:29907-29914, 2000.

Anthony TL, KL Pierce, JW Regan. Characterization of EP prostanoid receptor subtypes in primary cultures of bovine ciliary epithelial cells by immunofluorescent microscopy and functional studies. Curr Eye Res 20:394-404, 2000.

Woodward DF, et al. Replacement of the carboxylic acid group of prostaglandin F2a with a hydroxyl or methoxy substituent provides biologically unique compounds. Brit J Pharmacol 130:1933-1943, 2000.

Anthony TL, HL Brooks, D Boassa, S Leonov, G. Yanochko JW Regan, AJ Yool. Cloned human aquaporin-1 is a cyclic-GMP gated ion channel. Mol Pharmacol 57:576-588, 2000.

Fujino H, D Srinivasan, KL Pierce, JW Regan. Differential regulation of FP prostanoid receptor isoforms by protein kinase C. Mol Pharmacol 57:353-358, 2000.

Brooks HL, JW Regan, AJ Yool. Inhibition of aquaporin-1 water permeability by TEA: Involvement of the loop E pore region. Mol Pharmacol 57:1021-1026, 2000.

Fraeyman N, P Vanscheeuwijck, JM Wang, Y Huang, WP DePotter, JW Regan. Changes in the expresion of a2-adrenergic receptor subtypes during maturation of neuronal cells from fetal pig superior cervical ganglia. Develop Brain Res 116:127-132, 1999.

Hoyer PB, SL Marion, I Stine, BR Rueda, DL Hamernik, JW Regan, ME Wise. Ovine prostaglandin F2a receptor: steroid influence on steady state levels of luteal mRNA. Endocrine 10:105-111, 1999.

Pierce KL, H Fujino, D Srinivasan, JW Regan. Activation of FP prostanoid receptor isoforms leads to rho-mediated changes in cell morphology and in the cell cytoskeleton. J Biol Chem 274:35944-35949, 1999.

Publications
Originally posted: September 9, 2013
Last updated: September 3, 2015
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