A vitamin D receptor-Ser/Thr phosphatase-p70 S6 kinase complex and modulation of its enzymatic activities by the ligand.
We provide evidence of a cross-talk between nuclear receptor and Ser/Thr protein phosphatases and show that vitamin D receptor (VDR) interacts with the catalytic subunit of protein phosphatases, PP1c and PP2Ac, and induces their enzymatic activity in a ligand-dependent manner. PP1c specifically interacts with VDR but not retinoic acid receptor ... alpha and retinoid X receptor alpha in yeast. Although VDR-PP1c and VDR-PP2Ac interaction is ligand-independent in vivo, 1alpha,25-dihydroxy-vitamin D(3) induces VDR-associated phosphatase activity. Further, VDR modulation of PP1c/PP2Ac activity results in a rapid and specific dephosphorylation and inactivation of their substrate, p70 S6 kinase (p70(S6k)). Finally, we demonstrate that the endogenous VDR, PP1c or PP2Ac, and p70(S6k) are present in a ternary complex in vivo, and the interaction of p70(S6k) with the VDR-PP complex is modulated by the phosphorylation state of the kinase. Since p70(S6k) is essential for G(1)-S transition, our results provide a molecular basis of 1alpha,25-dihydroxyvitamin D(3)-induced G(1) block in colon cancer cells.
Mesh Terms:
G1 Phase, Humans, Ligands, Phosphoprotein Phosphatases, Phosphorylation, Protein Phosphatase 1, Receptors, Calcitriol, Ribosomal Protein S6 Kinases, Tumor Cells, Cultured
G1 Phase, Humans, Ligands, Phosphoprotein Phosphatases, Phosphorylation, Protein Phosphatase 1, Receptors, Calcitriol, Ribosomal Protein S6 Kinases, Tumor Cells, Cultured
J. Biol. Chem.
Date: Jul. 12, 2002
PubMed ID: 12036952
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