Stimulation of phosphorylation of mitogen-activated protein kinase by 1alpha,25-dihydroxyvitamin D3 in promyelocytic NB4 leukemia cells: a structure-function study

Endocrinology
X SongA W Norman

Abstract

Recent studies have shown that 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2D3] actions in cell growth and differentiation are mediated by both its nuclear receptor (VDRnuc) and its rapid membrane-related effects. In the present study, we investigated the effect of 1alpha,25-(OH)2D3 on p42mapk phosphorylation using human acute promyelocytic leukemia cells (NB4). 1Alpha,25-(OH)2D3 (10[-8] M) significantly increased p42mapk phosphorylation in a time- and dose-dependent manner, with the earliest response detectable at 30 sec. Because 1alpha,25-(OH)2D3 is a conformationally flexible molecule, we have used a series of conformationally locked (6-s-cis vs. 6-s-trans) analogs to evaluate which shape is optimal for activation. Four 6-s-cis-locked analogs (HF, JM, JN, and JP) and two 6-s-trans-locked analog (JB and JD) were studied. HF, JM, JN, and JP all increased p42mapk phosphorylation at 1 and 5 min (10[-8] M), but JB and JD had little effect. Analog HL [1beta,25-(OH)2D3], a specific antagonist for only the rapid effects of 1alpha,25-(OH)2D3, attenuated 1alpha,25-(OH)2D3-induced p42mapk phosphorylation 65-90%. To assess the potential involvement of the VDRnuc in mediating the analog's action, the relative abilities of the analogs to...Continue Reading

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Citations

Feb 6, 2004·Proceedings of the National Academy of Sciences of the United States of America·Laura P Zanello, Anthony W Norman
Aug 25, 2004·Proceedings of the National Academy of Sciences of the United States of America·Mathew T MizwickiAnthony W Norman
May 17, 2012·Pharmacogenetics and Genomics·Audrey H PoonTeri E Klein
Dec 14, 2001·Biochemical and Biophysical Research Communications·C BuitragoR Boland
Dec 7, 2007·Biogerontology·Verónica González PardoAna Russo de Boland
Nov 15, 2002·Molecular and Cellular Endocrinology·Anthony W NormanHelen L Henry
Jan 15, 2008·International Urology and Nephrology·George RammosStavroula Ziakka
Mar 23, 2010·The Journal of Steroid Biochemistry and Molecular Biology·Guisheng Zhao, Robert U Simpson
Sep 16, 2004·Journal of Cellular Biochemistry·Daniela A CapiatiRicardo L Boland
Dec 17, 2015·Antimicrobial Agents and Chemotherapy·Guang-Sheng LeiChao-Hung Lee
Oct 8, 2008·The Journal of Physiological Sciences : JPS·Kukiat TudporNarattaphol Charoenphandhu
Jun 14, 2005·American Journal of Physiology. Renal Physiology·Adriana S DussoEduardo Slatopolsky
Aug 10, 2010·Acta Crystallographica. Section D, Biological Crystallography·Shinji KakudaMidori Takimoto-Kamimura
Jan 7, 2004·Nature Reviews. Drug Discovery·Anthony W NormanDerek P G Norman
Jul 8, 2015·Chinese Medical Sciences Journal = Chung-kuo I Hsüeh K'o Hsüeh Tsa Chih·Ying FanXiao-ni Yan
Jun 8, 2000·The Journal of Clinical Endocrinology and Metabolism·E FalkensteinM Wehling
Aug 27, 1999·Journal of Cellular Biochemistry·V Le MellayM Lieberherr
Jul 5, 2003·Physiological Reviews·Ralf M LoselMartin Wehling
Dec 3, 2016·Hormone Molecular Biology and Clinical Investigation·Pablo R Costanzo, Pablo Knoblovits
Apr 3, 2001·European Journal of Clinical Investigation·E Falkenstein, M Wehling
Aug 28, 2004·The Journal of Biological Chemistry·Ramesh NarayananNancy L Weigel

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