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.
Conflict of interest statement
Conflicts of interest None.
Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGRalphaR477H and hGRalphaG679S associated with generalized glucocorticoid resistance.J Clin Endocrinol Metab. 2006 Apr;91(4):1535-43. doi: 10.1210/jc.2005-1893. Epub 2006 Jan 31. J Clin Endocrinol Metab. 2006. PMID: 16449337
The human glucocorticoid receptor (hGR) beta isoform suppresses the transcriptional activity of hGRalpha by interfering with formation of active coactivator complexes.Mol Endocrinol. 2005 Jan;19(1):52-64. doi: 10.1210/me.2004-0112. Epub 2004 Sep 30. Mol Endocrinol. 2005. PMID: 15459252
Human glucocorticoid receptor alpha transcript splice variants with exon 2 deletions: evidence for tissue- and cell type-specific functions.Biochemistry. 2005 May 24;44(20):7395-405. doi: 10.1021/bi047485e. Biochemistry. 2005. PMID: 15895983
The physiology of human glucocorticoid receptor beta (hGRbeta) and glucocorticoid resistance.Ann N Y Acad Sci. 2006 Jun;1069:1-9. doi: 10.1196/annals.1351.001. Ann N Y Acad Sci. 2006. PMID: 16855130 Review.
Protein Palmitoylation by DHHC Protein Family.In: Kittler JT, Moss SJ, editors. The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology. Boca Raton (FL): CRC Press/Taylor & Francis; 2006. Chapter 5. The Dynamic Synapse: Molecular Methods in Ionotropic Receptor Biology. 2006. PMID: 21204476 Free Books & Documents. Review.
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