Vitamin K-dependent gamma-carboxylation of the 1,25-dihydroxyvitamin D3 receptor.
It has been reported that vitamin K deficiency in the rat markedly increases the 1,25-dihydroxyvitamin D3 receptor (VDR) binding to DNA and that vitamin K-dependent gamma-carboxylation of endogenous substrates of the intestinal and renal cytosol, also containing VDR, sharply reduced that binding (Sergeev, I.N., and Spirichev, V.B. (1989) Nutr. Res. 9, 725-733). In the present study we have evaluated vitamin K-dependent 14CO2 incorporation to VDR quantitated by immunoprecipitation with anti-VDR monoclonal antibodies. The results obtained strongly suggest that VDR in vitro can undergo gamma-carboxylation in the presence of vitamin K1 and that 15-25% of Glu residues in the VDR are carboxylated in vivo. Taking into account our earlier findings, it is likely that the VDR gamma-carboxylation modulates its binding to DNA.
Sergeev
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IN
Department of Biochemistry, University of California, Riverside 92521.
Norman
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D000818:Animals; D000911:Antibodies, Monoclonal; D002117:Calcitriol / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002645:Chickens; D002762:Cholecalciferol / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid / Q000187:drug effects / Q000378:metabolism*; D014808:Vitamin D Deficiency / Q000378:metabolism; D014812:Vitamin K / Q000037:antagonists & inhibitors* / Q000502:physiology*; D014859:Warfarin / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D002250:Carbon Radioisotopes; D018167:Receptors, Calcitriol; D011987:Receptors, Steroid; D014812:Vitamin K; D002245:Carbon Dioxide; D002762:Cholecalciferol; D014859:Warfarin; D002117:Calcitriol