人糖皮质激素受体（hGR）的S-棕榈酰化在介导非基因组糖皮质激素作用中的作用
The Role of S-Palmitoylation of the Human Glucocorticoid Receptor (hGR) in Mediating the Nongenomic Glucocorticoid Actions.
作者信息
Nicolaides Nicolas C, Kino Tomoshige, Roberts Michael L, Katsantoni Eleni, Sertedaki Amalia, Moutsatsou Paraskevi, Psarra Anna-Maria G, Chrousos George P, Charmandari Evangelia
机构信息
Division of Endocrinology and Metabolism, Center of Clinical, Experimental Surgery and Translational Research, Biomedical Research Foundation of the Academy of Athens, Athens, Greece.
Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, National and Kapodistrian University of Athens Medical School, "Aghia Sophia" Children's Hospital, Athens, Greece.
出版信息
J Mol Biochem. 2017;6(1):3-12. Epub 2017 Apr 15.
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.
背景
许多快速的非基因组糖皮质激素作用是由膜结合糖皮质激素受体（GRs）介导的。S-棕榈酰化是一种脂质翻译后修饰，可介导某些类固醇受体的膜定位。人糖皮质激素受体α（hGRα）的配体结合域中存在一个高度同源的氨基酸序列（663YLCM KTLLL671），提示hGRα可能也会发生S-棕榈酰化。
目的
研究基序663YLCMKTLLL671在hGRα膜定位及介导快速非基因组糖皮质激素信号传导中的作用。
方法与结果
我们发现，突变受体hGRαY663A、hGRαC665A和hGRαLL670/671AA，以及添加棕榈酰化抑制剂2-溴棕榈酸酯，均未阻止hGRα的膜定位及其与小窝蛋白-1的共定位，且在早期时间点不影响丝裂原活化蛋白激酶（MAPK）信号通路的双相激活。最后，未显示hGRα发生S-棕榈酰化。
结论
基序663YLCMKTLLL671在hGRα的膜定位中不起作用，也不介导非基因组糖皮质激素作用。
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