Ligand modulates VDR-Ser/Thr protein phosphatase interaction and p70S6 kinase phosphorylation in a cell-context-dependent manner

The Journal of Steroid Biochemistry and Molecular Biology
David J BettounSunil Nagpal

Abstract

We have recently shown that in colon cancer cells, Vitamin D receptor (VDR) interacts with the catalytic subunit of Ser/Thr protein phosphatases, PP1c and PP2Ac, and induces their enzymatic activity in a ligand-dependent manner. The VDR-PP1c and VDR-PP2Ac interactions were ligand independent in vivo, and 1,25-dihydroxyvitamin D(3) (1,25(OH)(2)D(3))-mediated increase in VDR-associated phosphatase activity resulted in dephosphorylation and inactivation of p70S6 kinase in colon cancer cells. Here, we demonstrate that in myeloid leukemia cells, 1,25(OH)(2)D(3) treatment increased the Thr389 phosphorylation of p70S6 kinase. Accordingly, 1,25(OH)(2)D(3) decreased VDR-associated Ser/Thr protein phosphatase activity by dissociating VDR-PP1c and VDR-PP2Ac interactions. Further, 1,25(OH)(2)D(3) increased the association between VDR and Thr389 phosphorylated p70S6 kinase. Finally, by using non-secosteroidal VDR ligands, we demonstrate a separation between transactivation and p70S6 kinase phosphorylation activities of VDR and show pharmacologically that p70S6 kinase phosphorylation correlates with HL-60 cell differentiation.

References

Jul 7, 2001·Trends in Biochemical Sciences·M Bollen
Feb 7, 2003·Mini Reviews in Medicinal Chemistry·Karen V PinetteSunil Nagpal
Mar 15, 2003·Molecular Endocrinology·Amelia L M Sutton, Paul N MacDonald

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Citations

Nov 19, 2011·The Journal of Biological Chemistry·Mauricio Di FulvioJulian Gomez-Cambronero
May 14, 2010·PLoS Genetics·Jacques MontagneGeorge Thomas
May 22, 2013·The Journal of Cell Biology·Tiffiney R HartmanAlana M O'Reilly
May 4, 2007·Experimental Parasitology·Elmo Eduardo de Almeida-AmaralJosé Roberto Meyer-Fernandes
Nov 18, 2005·Experimental Parasitology·Fábio Vasconcelos FonsecaJosé Roberto Meyer-Fernandes
Aug 11, 2011·Experimental Parasitology·Rafael Paletta-SilvaJosé Roberto Meyer-Fernandes
Feb 9, 2007·Journal of Cellular Biochemistry·Meggan E ValranceJoellen Welsh

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