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Research Description:
Studies in the Friedman laboratory focus on the regulation of parathyroid hormone receptor signaling and regulated trafficking. PTH controls extracellular calcium and phosphate homeostasis. Its effects on kidney and bone are mediated by its cognate receptor, the type I PTH receptor (PTH1R). Key advances have been made in understanding cell-specific PTH1R signaling and trafficking, and recent observations indicate that PTH1R activation, desensitization and endocytosis are mediated through distinct structural states that derive from specific interactions between ligand and receptor. Agonist- or antagonist-occupied receptor states induce discrete conformations with accessibility to intracellular receptor domains. The differential or inducible involvement of these domains in coupling to G proteins may represent a molecular basis for ligand-selective responses not only for the PTH1R, but also for other G protein-coupled receptors. Current work is directed at elucidating the molecular and structural mechanisms of how cytoplasmic scaffold proteins such as NHERF1 and Dishevelled legislate cell-, ligand-, and stage-specific receptor trafficking.
Education:
B.A. (Zoology), Syracuse University, 1970.
Ph.D. (Pharmacology), SUNY Upstate Medical Center, 1975.
Postdoctoral Fellow (Pharmacology), University of Lausanne, Switzerland, 1975-1977.
Postdoctoral Fellow (Physiology), Cornell University Medical College, 1977-1979.
Important Publications:
- Bernardo JF, CE Magyar, WB Sneddon and PA Friedman. Impaired renal calcium absorption in mice lacking calcium channel ß3 subunits. Can J Physiol Pharmacol 87:522-530, 2009
- Gamba B and PA Friedman. Thick ascending limb: The Na+:K+:2Cl− cotransporter, NKCC2, and the calcium-sensing receptor, CaSR. Pflugers Arch 458:61-76, 2009
- Garrido JL, D Wheeler, LL Vega, PA Friedman and G Romero. Role of phospholipase D in parathyroid hormone receptor type 1 signaling and trafficking. Mol Endocrinol 23:2048-2059, 2009
- Wang B, Y Yang, AB Abou-Samra and PA Friedman. NHERF1 regulates parathyroid hormone receptor desensitization: Interference with ß-arrestin binding. Mol Pharmacol 75:1189-1197, 2009
- Bisello A and PA Friedman. PTH and PTHrP actions on kidney and bone. In Principles of Bone Biology (3 ed.), edited by JP Bilezikian, LG Raisz and TJ Martin, p. 665-712, 2008
- Sebastian EM, LJ Suva and PA Friedman. Differential effects of intermittent PTH(1-34) and PTH(7-34) on bone microarchitecture and aortic calcification in experimental renal failure. Bone 43:1022-1030, 2008
- Wang B, Y Yang and PA Friedman. NA/H exchange regulator factor 1, a novel Akt-associating protein, regulates extracellular signal-related signaling through a B-Raf-mediated pathway. Mol Biol Cell 19:1636-1644, 2008
- Wheeler D, JL Garrido, A Bisello, YK Kim, PA Friedman and G Romero. Regulation of PTH1R dynamics, traffic and signaling by the NA+/H+ exchanger regulatory factor-1 (NHERF1) in rat osteosarcoma ROS 17/28 cells. Mol Endocrinol 22:1163-1170, 2008
- Wang B, A Bisello, Y Yang, GG Romero and PA Friedman. NHERF1 regulates parathyroid hormone receptor membrane retention without affecting recycling. J Biol Chem 282:36214-36222, 2007
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