Distinct receptor activity-modifying protein domains differentially modulate interaction with calcitonin receptors

Molecular Pharmacology
Madhara UdawelaPatrick M Sexton

Abstract

Calcitonin receptors (CTRs) dimerize with receptor activity-modifying proteins (RAMPs) to generate high-affinity amylin (AMY) receptors; however, the relative contribution of individual RAMP domains to the formation of AMY receptors is poorly understood. We have used chimeras between RAMP1 and RAMP2 that specifically exchanged the N-terminal, transmembrane, or C-terminal domain and examined these in assays of [(125)I]amylin binding or peptide-induced cAMP signaling in COS-7 cells transiently transfected with wild-type or chimeric RAMPs and human CTRa. The specificity of peptides in competition for [(125)I]amylin binding was principally dictated by the N-terminal domain present in the chimeras; however, the maximal level of binding induced was dictated by the transmembrane domain present. This extended previous data (Zumpe et al., 2000) to provide a distinction between the transmembrane domain and the C terminus in this function. In contrast to the effects on binding, each of the RAMP domains played a role in the signaling phenotype of the receptors. In particular, the potency of calcitonin gene-related peptide (CGRP) was most influenced by the C-terminal domain present, in which the presence of the RAMP1 C-terminal domain led t...Continue Reading

References

Jan 7, 2000·Biochemical and Biophysical Research Communications·E T ZumpeP M Sexton
Feb 8, 2003·The Journal of Biological Chemistry·Timothy J FitzsimmonsStephen A Wank
May 6, 2004·Seminars in Cell & Developmental Biology·Madhara UdawelaPatrick M Sexton
Aug 23, 2005·Pharmacology & Therapeutics·Debbie L HayPatrick M Sexton

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Citations

Feb 4, 2010·Calcified Tissue International·Maria EllegaardMartin Stahlhut
Jul 18, 2009·Nature Reviews. Drug Discovery·Terry P Kenakin
Jul 8, 2009·Journal of Receptor and Signal Transduction Research·Terry Kenakin
Jan 8, 2016·Critical Reviews in Biochemistry and Molecular Biology·Klara R KleinKathleen M Caron
Oct 31, 2015·Annual Review of Pharmacology and Toxicology·Debbie L Hay, Augen A Pioszak
Jan 20, 2009·Drug Discovery Today·Patrick M SextonDebbie L Hay
Mar 23, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Rachel A Davey, David M Findlay
Jun 9, 2011·British Journal of Pharmacology·James BarwellDebbie L Hay
Oct 3, 2006·Trends in Biochemical Sciences·Narayanan Parameswaran, William S Spielman
Apr 5, 2016·Chemical Reviews·Denise WoottenPatrick M Sexton
Feb 11, 2012·Biochemical and Biophysical Research Communications·Kakon NagShigehisa Hirose
Apr 10, 2017·Molecular and Cellular Endocrinology·Sarah J RoutledgeDavid R Poyner
Dec 18, 2009·British Journal of Pharmacology·Tao Qi, Debbie L Hay
Jun 14, 2015·Pharmacological Reviews·Debbie L HayJonathan D Roth
Feb 5, 2015·The Journal of Pharmacology and Experimental Therapeutics·Emma T van der WesthuizenArthur Christopoulos
Apr 14, 2016·Biochemical Society Transactions·Debbie L HayDavid R Poyner
Jul 23, 2015·The Journal of Biological Chemistry·Cathryn WestonGraham Ladds
Aug 17, 2006·Molecular Pharmacology·Madhara UdawelaPatrick M Sexton
Mar 18, 2021·The Journal of Pharmacology and Experimental Therapeutics·Madeleine M FletcherPatrick M Sexton

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