Email the author The Role of S-Palmitoylation of the Human Glucocorticoid Receptor (hGR) in Mediating the Nongenomic Glucocorticoid Actions
Abstract
Background: Many rapid nongenomic glucocorticoid actions are mediated by membrane-bound glucocorticoid receptors (GRs). S-palmitoylation is a lipid post-translational modification that mediates the membrane localization of some steroid receptors. A highly homologous amino acid sequence (663YLCM KTLLL671) is present in the ligand-binding domain of hGRα, suggesting that hGRα might also undergo S-palmitoylation.
Aim: To investigate the role of the motif 663YLCMKTLLL671 in membrane localization of the hGRα and in mediating rapid nongenomic glucocorticoid signaling.
Methods and Results: We showed that the mutant receptors hGRαY663A, hGRαC665A and hGRαLL670/671AA, and the addition of the palmitoylation inhibitor 2-bromopalmitate did not prevent membrane localization of hGRα and co-localization with caveolin-1, and did not influence the biphasic activation of mitogen-activated protein kinase (MAPK) signaling pathway in the early time points. Finally, the hGRα was not shown to undergo S-palmitoylation.
Conclusions: The motif 663YLCMKTLLL671 does not play a role in membrane localization of hGRα and does not mediate the nongenomic glucocorticoid actions.
Â
Â
Keywords
References
Ayroldi E, Cannarile L, Migliorati G, Nocentini G, Delfino DV & Riccardi C 2012 Mechanisms of the anti-inflammatory effects of glucocorticoids: genomic and nongenomic interference with MAPK signaling pathways. FASEB J 26 4805-4820
Bellavance MA & Rivest S 2012 The neuroendocrine control of the innate immune system in health and brain diseases. Immunol Rev 248 36-55
Charmandari E, Tsigos C & Chrousos GP 2005 Endocrinology of the stress response. Annu Rev Physiol 67 259-284
Chrousos GP, Charmandari E & Kino T 2004 Glucocorticoid action networks-an introduction to systems biology. J Clin Endocrinol Metab 89 563-564
Chrousos GP & Kino T 2005 Intracellular glucocorticoid signaling: a formerly simple system turns stochastic. Sci STKE 2005 pe48
Chrousos GP & Kino T 2007 Glucocorticoid action networks and complex psychiatric and /or somatic disorders. Stress 10 213-219
Deng Q, Waxse B, Riquelme D, Zhang J & Aguilera G 2015 Helix 8 of the ligand binding domain of the glucocorticoid receptor (GR) is essential for ligand binding. Mol Cell Endocrinol 408 23-32
Duvernay MT, Zhou F & Wu G 2004 A conserved motif for the transport of G protein-coupled receptors from the endoplasmic reticulum to the cell surface. J Biol Chem 279 30741-30750
Hafezi-Moghadam A, Simoncini T, Yang Z, Limbourg FP, Plumier JC, Rebsamen MC, Hsieh CM, Chui DS, Thomas KL, Prorock AJ, Laubach VE, Moskowitz MA, French BA, Ley K& Liao JK 2002 Acute cardiovascular protective effects of corticosteroids are mediated by non-transcriptional activation of endothelial nitric oxide synthase. Nat Med 8 473-479
Hinz B & Hirschelmann R 2000 Rapid non-genomic feedback effects of glucocorticoids on CRF-induced ACTH secretion in rats. Pharm Res 17 1273-1277
Karst H, Berger S, Turiault M, Tronche F, Schütz G & Joëls M 2005 Mineralocorticoid receptors are indispensable for nongenomic modulation of hippocampal glutamate transmission by corticosterone. Proc Natl Acad Sci U S A 102 19204-19207
Lee SR, Kim HK, Youm JB, Dizon LA, Song IS, Jeong SH, Seo DY, Ko KS, Rhee BD, Kim N & Han J 2012 Non-genomic effect of glucocorticoids on cardiovascular system. Pflugers Arch 464 549-559
Linder ME & Deschenes RJ 2007 Palmitoylation: policing protein stability and traffic. Nat Rev Mol Cell Biol 8 74-84
Losel R & Wehling M 2003 Nongenomic actions of steroid hormones. Nat Rev Mol Cell Biol 4 46-56
Löwenberg M, Verhaar AP, Bilderbeek J, Marle Jv, Buttgereit F, Peppelenbosch MP, van Deventer SJ & Hommes DW 2006 Glucocorticoids cause rapid dissociation of a T-cell-receptor-associated protein complex containing LCK and FYN. EMBO Rep 7 1023-1029
Marino M & Ascenzi P 2006 Steroid hormone rapid signaling: the pivotal role of S-palmitoylation. IUBMB Life 58 716-719
Marino M, Ascenzi P & Acconcia F 2006 S-palmitoylation modulates estrogen receptor alpha localization and functions. Steroids 71 298-303
Nicolaides NC, Galata Z, Kino T, Chrousos GP & Charmandari E 2010 The human glucocorticoid receptor: Molecular basis of biologic function. Steroids 75 1-12.
Pedram A, Razandi M, Deschenes RJ & Levin ER 2012 DHHC-7 and -21 are palmitoylacyltransferases for sex steroid receptors. Mol Biol Cell 23 188-199
Pedram A, Razandi M, Lewis M, Hammes S & Levin ER 2014 Membrane-localized estrogen receptor α is required for normal organ development and function. Dev Cell 29 482-490
Pedram A, Razandi M, O'Mahony F, Harvey H, Harvey BJ & Levin ER 2013 Estrogen reduces lipid content in the liver exclusively from membrane receptor signaling. Sci Signal 6 ra36
Pedram A, Razandi M, Sainson RC, Kim JK, Hughes CC & Levin ER 2007 A conserved mechanism for steroid receptor translocation to the plasma membrane. J Biol Chem 282 22278-22288
Razandi M, Pedram A & Levin ER 2010 Heat shock protein 27 is required for sex steroid receptor trafficking to and functioning at the plasma membrane. Mol Cell Biol 30 3249-3261
Rhen T & Cidlowski JA 2005 Anti-inflammatory action of glucocorticoids-new mechanisms for old drugs. N Engl J Med 353 1711-1723
Samarasinghe RA, Di Maio R, Volonte D, Galbiati F, Lewis M, Romero G & DeFranco DB 2011 Nongenomic glucocorticoid receptor action regulates gap junction intercellular communication and neural progenitor cell proliferation. Proc Natl Acad Sci U S A 108 16657-16662
Song IH & Buttgereit F 2006 Non-genomic glucocorticoid effects to provide the basis for new drug developments. Mol Cell Endocrinol 246 142-146
Stellato C 2004 Post-transcriptional and nongenomic effects of glucocorticoids. Proc Am Thorac Soc 1 255-263
Refbacks
- There are currently no refbacks.
Copyright © 2021 Journal of Molecular Biochemistry