Phosphorylation of serine 208 in the human vitamin D receptor. The predominant amino acid phosphorylated by casein kinase II, in vitro, and identification as a significant phosphorylation site in intact cells.

P.W. Jurutka; J.C. Hsieh; P.N. MacDonald; C.M. Terpening; C.A. Haussler; M.R. Haussler; G.K. Whitfield

doi:10.1016/S0021-9258(18)53319-6

Journal Article| Volume 268, ISSUE 9, P6791-6799, March 25, 1993

Phosphorylation of serine 208 in the human vitamin D receptor. The predominant amino acid phosphorylated by casein kinase II, in vitro, and identification as a significant phosphorylation site in intact cells.

P.W. Jurutka
P.W. Jurutka
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
J.C. Hsieh
J.C. Hsieh
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
P.N. MacDonald
P.N. MacDonald
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
C.M. Terpening
C.M. Terpening
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
C.A. Haussler
C.A. Haussler
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
M.R. Haussler
M.R. Haussler
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author
G.K. Whitfield
G.K. Whitfield
Affiliations
Department of Biochemistry, College of Medicine, University of Arizona, Tucson 85724.
Search for articles by this author

Open AccessPublished:March 25, 1993DOI:https://doi.org/10.1016/S0021-9258(18)53319-6

This paper is only available as a PDF. To read, Please Download here.

The human 1,25-dihydroxyvitamin D3 receptor (hVDR), like other members of the steroid/thyroid receptor superfamily, has been observed to undergo rapid phosphorylation. We report here that the hVDR is a substrate for casein kinase II (CK-II), a regulatory enzyme of significance in the function of nuclear proteins. Intact hVDRs produced by in vitro transcription/translation or in a baculovirus overexpression system served as efficient substrates for purified bovine CK-II, and the magnitude of this phosphorylation was not affected by the addition of 1,25-dihydroxyvitamin D3. CK-II-catalyzed phosphorylation of truncated hVDRs suggested that phosphorylated residues may occur between Arg121 and Asp232, including the region of hVDR which we have previously demonstrated to contain a major site(s) of phosphorylation in intact cells (Jones, B.B., Jurutka, P.W., Haussler, C.A., Haussler, M.R., and Whitfield, G.K. (1991) Mol. Endocrinol. 5, 1137-1146). Site-directed mutagenesis of serine/threonine residues in this region now reveals a site of phosphorylation at Ser208 contained within the sequence -S208 (P)EEDSDD-, a classic CK-II consensus recognition site. Mutation of this serine to a glycine drastically reduces phosphorylation of hVDR by CK-II, in vitro. The Ser208 mutant receptor also shows a dramatic decrease in [32P]orthophosphate incorporation when transfected into COS-7 cells. We therefore propose that phosphorylation of hVDR at Ser208 in target cells is mediated by casein kinase II or a similar enzyme, and that this quantitatively significant post-translational modification is a potential mechanism for the modulation of the activity of hVDR in controlling gene transcription.

References

- Evans R.M.
Science. 1988; 240: 889-895
- Google Scholar
- Beato M.
Cell. 1989; 56: 335-344
- Google Scholar
- Hauasler M.R.
- Mangelsdorf D.J.
- Komm B.S.
- Terpening C.M.
- Yamaoka K.
- Allegretto E.A.
- Baker A.R.
- Shine J.
- McDonnell D.P.
- Hughes M.
- Weigel N.L.
- O'Malley B.W.
- Pike J.W.
Recent Prog. Horm. Res. 1988; 44: 263-305
- Google Scholar
- Orti E.
- Bodwell J.E.
- Munck A.
Endocr. Rev. 1992; 13: 105-128
- Google Scholar
- Denner L.A.
- Weigel N.L.
- Maxwell B.L.
- Schrader W.T.
- O'Malley B.W.
Science. 1990; 250: 1740-1743
- Google Scholar
- Denner L.A.
- Schrader W.T.
- O'Malley B.W.
- Weigel N.L.
J. Biol. Chem. 1990; 265: 16548-16555
- Google Scholar
- Bodwell J.E.
- Orti E.
- Coull J.M.
- Pappin D.J.C.
- Smith L.I.
- Swift F.
J. Biol. Chem. 1991; 266: 7549-7555
- Google Scholar
- Goldberg Y.
- Glineur C.
- Gesquière J.-C.
- Ricouart A.
- Sap J.
- Vennström B.
- Ghysdael J.
EMBO J. 1988; 7: 2425-2433
- Google Scholar
- Glineur C.
- Bailly M.
- Ghysdael J.
Oncogene. 1989; 4: 1247-1254
- Google Scholar
- Pike J.W.
- Sleator N.M.
Biochem. Biophys. Res. Commun. 1985; 131: 378-385
- Google Scholar
- Brown T.A.
- DeLuca H.F.
J. Biol. Chem. 1990; 265: 10025-10029
- Google Scholar
- Jones B.B.
- Jurutka P.W.
- Haussler C.A.
- Haussler M.R.
- Whitfield G.K.
Mol. Endocrinol. 1991; 5: 1137-1146
- Google Scholar
- Marin O.
- Meggio F.
- Marchiori F.
- Borin G.
- Pinna L.A.
Eur. J. Biochem. 1986; 160: 239-244
- Google Scholar
- Edelman A.M.
- Blumenthal D.K.
- Krebs E.G.
Annu. Rev. Biochem. 1987; 56: 567-613
- Google Scholar
- Durban E.
- Goodenough M.
- Mills J.
- Busch H.
EMBO J. 1985; 4: 2921-2926
- Google Scholar
- Ackerman P.
- Glover C.V.C.
- Osheroff N.
J. Biol. Chem. 1988; 263: 12653-12660
- Google Scholar
- Dahmus M.E.
J. Biol. Chem. 1981; 256: 3332-3339
- Google Scholar
- Stetler D.A.
- Rose K.M.
Biochemistry. 1982; 21: 3721-3728
- Google Scholar
- Lüscher B.
- Kuenzel E.A.
- Krebs E.G.
- Eisenman R.N.
EMBO J. 1989; 8: 1111-1119
- Google Scholar
- Lüscher B.
- Christenson E.
- Litchfield D.W.
- Krebs E.G.
- Eisenman R.N.
Nature. 1990; 344: 517-522
- Google Scholar
- Krebs E.G.
- Eisenman R.N.
- Kuenzel E.A.
- Litchfield D.W.
- Lozeman F.J.
- Lüscher B.
- Sommercorn J.
Cold Spring Harbor Symp. Quant. Biol. 1988; 53: 77-84
- Google Scholar
- Baker A.R.
- McDonnell D.P.
- Hughes M.
- Crisp T.M.
- Mangelsdorf D.J.
- Haussler M.R.
- Pike J.W.
- Shine J.
- O'Malley B.W.
Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 3294-3298
- Google Scholar
- Terpening C.M.
- Haussler M.R.
Biochem. Biophys. Res. Commun. 1990; 173: 1129-1136
- Google Scholar
- MacDonald P.N.
- Haussler C.A.
- Terpening C.M.
- Galligan M.A.
- Reeder M.C.
- Whitfield G.K.
- Haussler M.R.
J. Biol. Chem. 1991; 266: 18808-18813
- Google Scholar
- Mangelsdorf D.J.
- Pike J.W.
- Haussler M.R.
Proc. Natl. Acad. Sci. U. S. A. 1987; 84: 354-358
- Google Scholar
- Pike J.W.
- Marion S.L.
- Donaldson C.A.
- Haussler M.R.
J. Biol. Chem. 1983; 258: 1289-1296
- Google Scholar
- Litchfield D.W.
- Lozeman F.J.
- Piening C.
- Sommercorn J.
- Takio K.
- Walsh K.A.
- Krebs E.G.
J. Biol. Chem. 1990; 265: 7638-7644
- Google Scholar
- Kunkel T.A.
- Roberts J.D.
- Zakour R.A.
Methods Enzymol. 1987; 154: 367-382
- Google Scholar
- Green S.
- Isseman I.
- Sheer E.
Nucleic Acids Res. 1988; 16: 369
- Google Scholar
- Gluzman Y.
Cell. 1981; 23: 175-182
- Google Scholar
- Kingston R.E.
Ausubel F.M. Brent R. Kingston R.E. Moore D.D. Siedman J.G. Smith J.A. Struhl K. Current Protocols in Molecular Biology. Greene Publishing and Wiley-Interscicncc, New York1990: 9.1.1-9.1.4
- Google Scholar
- Mangelsdorf D.J.
- Komm B.S.
- McDonnell D.P.
- Pike J.W.
- Haussler M.R.
Biochemistry. 1987; 26: 8332-8338
- Google Scholar
- Hathaway G.M.
- Traugh J.A.
Curr. Top. Cell. Regul. 1982; 21: 101-127
- Google Scholar
- Pike J.W.
- Haussler M.R.
Proc. Natl. Acad. Sci. U. S. A. 1979; 76: 5485-5489
- Google Scholar
- Haussler M.R.
- Terpening C.M.
- Komm B.S.
- Whitfield G.K.
- Haussler C.A.
Norman A.W. Schaefer K. Grigoleit H.-G. von Herrath D. Vitamin D: Molecular, Cellular, and Clinical Endocrinology. Walter de Gruyter & Co., Berlin1988: 205-214
- Google Scholar
- Burmester J.K.
- Wiese R.J.
- Maeda N.
- DeLuca H.F.
Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 9499-9502
- Google Scholar
- Struhl K.
Cell. 1987; 49: 295-297
- Google Scholar
- Prives C.
Cell. 1990; 61: 735-738
- Google Scholar
- Figge J.
- Webster T.
- Smith T.F.
- Paucha E.
J. Virol. 1988; 62: 1814-1818
- Google Scholar
- Grässer F.A.
- Scheidtmann K.H.
- Tuazon P.T.
- Traugh J.A.
- Walter G.
Virology. 1988; 165: 13-22
- Google Scholar
- Lin A.
- Frost J.
- Deng T.
- Smeal T.
- Al-Alawi N.
- Kikkawa U.
- Hunter T.
- Brenner D.
- Karin M.
Cell. 1992; 70: 777-789
- Google Scholar
- Berberich S.J.
- Cole M.D.
Genes & Dev. 1992; 6: 166-176
- Google Scholar
- Hsieh J.-C.
- Jurutka P.W.
- Galligan M.A.
- Terpening C.M.
- Haussler C.A.
- Samuels D.S.
- Shimizu Y.
- Shimizu N.
- Haussler M.R.
Proc. Natl. Acad. Sci. U. S. A. 1991; 88: 9315-9319
- Google Scholar
- Glineur C.
- Zenke M.
- Beug H.
- Ghysdael J.
Genes & Dev. 1990; 4: 1663-1676
- Google Scholar
- Hall F.L.
- Braun R.K.
- Mihara K.
- Fung Y.-K. T.
- Berndt N.
- Carbonaro-Hall D.A.
- Vulliet P.R.
J. Biol. Chem. 1991; 266: 17430-17440
- Google Scholar
- Draetta G.
Trends Biochem. Sci. 1990; 15: 378-383
- Google Scholar
- Boulton T.G.
- Nye S.H.
- Robbins D.J.
- Ip N.Y.
- Radziejewska E.
- Morgenbesser S.D.
- DePinho R.A.
- Panayotatos N.
- Cobb M.H.
- Yancopoulos G.D.
Cell. 1991; 65: 663-675
- Google Scholar
- Rossomando A.J.
- Sanghera J.S.
- Marsden L.A.
- Weber M.J.
- Pelech S.L.
- Sturgill T.W.
J. Biol. Chem. 1991; 266: 20270-20275
- Google Scholar
- Litchfield D.W.
- Lozeman F.J.
- Cicirelli M.F.
- Harrylock M.
- Ericsson L.H.
- Piening C.J.
- Krebs E.G.
J. Biol. Chem. 1991; 266: 20380-20389
- Google Scholar
- McDonnell D.P.
- Scott R.A.
- Kerner S.A.
- O'Malley B.W.
- Pike J.W.
Mol. Endocrinol. 1989; 3: 635-644
- Google Scholar
- Power R.F.
- Mani S.K.
- Codina J.
- Conneely O.M.
- O'Malley B.W.
Science. 1991; 254: 1636-1639
- Google Scholar
- Power R.F.
- Lydon J.P.
- Conneely O.M.
- O'Malley B.W.
Science. 1991; 252: 1546-1548
- Google Scholar
- Jurutka P.W.
- MacDonald P.N.
- Hsieh J.-C.
- Haussler M.R.
- Whitfield G.K.
J. Bone Miner. Res. 1992; 7 (abstr.): S108
- Google Scholar
- Pike J.W.
- Kesterson R.A.
- Scott R.A.
- Kerner S.A.
- McDonnell D.P.
- O'Malley B.W.
Norman A.W. Schaefer K. Grigoleit H.-G. von Herrath D. Vitamin D: Molecular, Cellular and Clinical Endocrinology. Walter de Gruyter & Co., Berlin1988: 215-224
- Google Scholar
- Pike J.W.
J. Biol. Chem. 1984; 259: 1167-1173
- Google Scholar

Article info

Publication history

Published online: March 25, 1993

Identification

DOI: https://doi.org/10.1016/S0021-9258(18)53319-6

Copyright

User license

Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |

How you can reuse Information Icon

ScienceDirect

Access this article on ScienceDirect

Toggle Thumbstrip

Property	Value
Status
Version
Ad File
Disable Ads Flag
Environment
Moat Init
Moat Ready
Contextual Ready
Contextual URL
Contextual Initial Segments
Contextual Used Segments
AdUnit
SubAdUnit
Custom Targeting
Ad Events
Invalid Ad Sizes

Phosphorylation of serine 208 in the human vitamin D receptor. The predominant amino acid phosphorylated by casein kinase II, in vitro, and identification as a significant phosphorylation site in intact cells.

References

Article info

Publication history

Identification

Copyright

User license

Permitted

For non-commercial purposes:

Not Permitted

ScienceDirect

Related Articles