This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints, Permissions and Rights Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, Y. Articles by Weigel, N. L. Search for Related Content PubMed PubMed Citation Articles by Zhang, Y. Articles by Weigel, N. L.

Phosphorylation of Human Progesterone Receptor by Cyclin-Dependent Kinase 2 on Three Sites That Are Authentic Basal Phosphorylation Sites In Vivo

Department of Cell Biology (Y.Z., A.P., J.P.C., N.L.W), Baylor College of Medicine, Houston, Texas 77030,
Department of Pathology and Molecular Biology Program, (C.A.B., P.P., D.P.E.), University of Colorado Health Sciences Center, Denver, Colorado 80262,
Department of Food Science and Technology (T-T.Y., W.H.), University of California at Davis, Davis, California 95616

The human progesterone receptor (hPR) in T47D breast cancer cells is phosphorylated on at least nine different serine residues. We have previously reported the identification of five sites; three are hormone inducible (Ser¹⁰², Ser²⁹⁴ and Ser³⁴⁵), and their phosphorylation correlates with the timing of the change in receptor mobility on gel electrophoresis in response to hormone treatment. The other two sites, Ser⁸¹ and Ser¹⁶², along with the remaining sites, are basally phosphorylated and exhibit a general increase in phosphorylation in response to hormone. With the exception of Ser⁸¹, all of these sites are in Ser-Pro motifs, suggesting that proline-directed kinases are responsible for their phosphorylation. We now report that cyclin A-cyclin-dependent kinase-2 complexes phosphorylate hPR-B in vitro with a high stoichiometry on three sites that are authentic basal sites in vivo. One of these is Ser¹⁶², which has been described previously. The other two sites are identified here as Ser¹⁹⁰ and Ser⁴⁰⁰. The specificity and stoichiometry of the in vitro phosphorylation suggest that hPR phosphorylation may be regulated in a cell cycle-dependent manner in vivo.

This article has been cited by other articles:

				S. E. Wardell, R. Narayanan, N. L. Weigel, and D. P. Edwards Partial Agonist Activity of the Progesterone Receptor Antagonist RU486 Mediated by an Amino-Terminal Domain Coactivator and Phosphorylation of Serine400 Mol. Endocrinol., February 1, 2010; 24(2): 335 - 345. [Abstract] [Full Text] [PDF]

				B.-S. An, S. L. Poon, W.-K. So, G. L. Hammond, and P. C.K. Leung Rapid Effect of GNRH1 on Follicle-Stimulating Hormone Beta Gene Expression in LbetaT2 Mouse Pituitary Cells Requires the Progesterone Receptor Biol Reprod, August 1, 2009; 81(2): 243 - 249. [Abstract] [Full Text] [PDF]

				E. J. Faivre, A. R. Daniel, C. J. Hillard, and C. A. Lange Progesterone Receptor Rapid Signaling Mediates Serine 345 Phosphorylation and Tethering to Specificity Protein 1 Transcription Factors Mol. Endocrinol., April 1, 2008; 22(4): 823 - 837. [Abstract] [Full Text] [PDF]

				H. Zong, Y. Chi, Y. Wang, Y. Yang, L. Zhang, H. Chen, J. Jiang, Z. Li, Y. Hong, H. Wang, et al. Cyclin D3/CDK11p58 Complex Is Involved in the Repression of Androgen Receptor Mol. Cell. Biol., October 15, 2007; 27(20): 7125 - 7142. [Abstract] [Full Text] [PDF]

				C.-S. Yang, H.-W. Xin, J. B. Kelley, A. Spencer, D. L. Brautigan, and B. M. Paschal Ligand Binding to the Androgen Receptor Induces Conformational Changes That Regulate Phosphatase Interactions Mol. Cell. Biol., May 1, 2007; 27(9): 3390 - 3404. [Abstract] [Full Text] [PDF]

				B.-S. An, D. M. Selva, G. L. Hammond, A. Rivero-Muller, N. Rahman, and P. C. K. Leung Steroid Receptor Coactivator-3 Is Required for Progesterone Receptor Trans-activation of Target Genes in Response to Gonadotropin-releasing Hormone Treatment of Pituitary Cells J. Biol. Chem., July 28, 2006; 281(30): 20817 - 20824. [Abstract] [Full Text] [PDF]

				D. A. Proia, B. W. Nannenga, L. A. Donehower, and N. L. Weigel Dual Roles for the Phosphatase PPM1D in Regulating Progesterone Receptor Function J. Biol. Chem., March 17, 2006; 281(11): 7089 - 7101. [Abstract] [Full Text] [PDF]

				N. R. Chapman, M. M. Kennelly, K. A. Harper, G. N. Europe-Finner, and S. C. Robson Examining the spatio-temporal expression of mRNA encoding the membrane-bound progesterone receptor-alpha isoform in human cervix and myometrium during pregnancy and labour Mol. Hum. Reprod., January 1, 2006; 12(1): 19 - 24. [Abstract] [Full Text] [PDF]

				D. A. Sarruf, I. Iankova, A. Abella, S. Assou, S. Miard, and L. Fajas Cyclin D3 Promotes Adipogenesis through Activation of Peroxisome Proliferator-Activated Receptor {gamma} Mol. Cell. Biol., November 15, 2005; 25(22): 9985 - 9995. [Abstract] [Full Text] [PDF]

				A. Skildum, E. Faivre, and C. A. Lange Progesterone Receptors Induce Cell Cycle Progression via Activation of Mitogen-Activated Protein Kinases Mol. Endocrinol., February 1, 2005; 19(2): 327 - 339. [Abstract] [Full Text] [PDF]

				R. Narayanan, A. A. Adigun, D. P. Edwards, and N. L. Weigel Cyclin-Dependent Kinase Activity Is Required for Progesterone Receptor Function: Novel Role for Cyclin A/Cdk2 as a Progesterone Receptor Coactivator Mol. Cell. Biol., January 1, 2005; 25(1): 264 - 277. [Abstract] [Full Text] [PDF]

				L. K. Pierson-Mullany and C. A. Lange Phosphorylation of Progesterone Receptor Serine 400 Mediates Ligand-Independent Transcriptional Activity in Response to Activation of Cyclin-Dependent Protein Kinase 2 Mol. Cell. Biol., December 15, 2004; 24(24): 10542 - 10557. [Abstract] [Full Text] [PDF]

				C. A. Lange Making Sense of Cross-Talk between Steroid Hormone Receptors and Intracellular Signaling Pathways: Who Will Have the Last Word? Mol. Endocrinol., February 1, 2004; 18(2): 269 - 278. [Abstract] [Full Text] [PDF]

				L. Labriola, M. Salatino, C. J. Proietti, A. Pecci, O. A. Coso, A. R. Kornblihtt, E. H. Charreau, and P. V. Elizalde Heregulin Induces Transcriptional Activation of the Progesterone Receptor by a Mechanism That Requires Functional ErbB-2 and Mitogen-Activated Protein Kinase Activation in Breast Cancer Cells Mol. Cell. Biol., February 1, 2003; 23(3): 1095 - 1111. [Abstract] [Full Text] [PDF]

				T. Shen, K. B. Horwitz, and C. A. Lange Transcriptional Hyperactivity of Human Progesterone Receptors Is Coupled to Their Ligand-Dependent Down-Regulation by Mitogen-Activated Protein Kinase-Dependent Phosphorylation of Serine 294 Mol. Cell. Biol., September 15, 2001; 21(18): 6122 - 6131. [Abstract] [Full Text] [PDF]

				D. L. Bain, M. A. Franden, J. L. McManaman, G. S. Takimoto, and K. B. Horwitz The N-terminal Region of the Human Progesterone A-receptor. STRUCTURAL ANALYSIS AND THE INFLUENCE OF THE DNA BINDING DOMAIN J. Biol. Chem., March 15, 2000; 275(10): 7313 - 7320. [Abstract] [Full Text] [PDF]

				C. A. Lange, T. Shen, and K. B. Horwitz Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome PNAS, February 1, 2000; 97(3): 1032 - 1037. [Abstract] [Full Text] [PDF]

				D. L. Clemm, L. Sherman, V. Boonyaratanakornkit, W. T. Schrader, N. L. Weigel, and D. P. Edwards Differential Hormone-Dependent Phosphorylation of Progesterone Receptor A and B Forms Revealed by a Phosphoserine Site-Specific Monoclonal Antibody Mol. Endocrinol., January 1, 2000; 14(1): 52 - 65. [Abstract] [Full Text]

				V. Giguère Orphan Nuclear Receptors: From Gene to Function Endocr. Rev., October 1, 1999; 20(5): 689 - 725. [Abstract] [Full Text]

				J. J. Brosens, N. Hayashi, and J. O. White Progesterone Receptor Regulates Decidual Prolactin Expression in Differentiating Human Endometrial Stromal Cells Endocrinology, October 1, 1999; 140(10): 4809 - 4820. [Abstract] [Full Text]

				I. Rogatsky, J. M. Trowbridge, and M. J. Garabedian Potentiation of Human Estrogen Receptor alpha Transcriptional Activation through Phosphorylation of Serines 104 and 106 by the Cyclin A-CDK2 Complex J. Biol. Chem., August 6, 1999; 274(32): 22296 - 22302. [Abstract] [Full Text] [PDF]

				D. Chen, P. E. Pace, R. C. Coombes, and S. Ali Phosphorylation of Human Estrogen Receptor alpha  by Protein Kinase A Regulates Dimerization Mol. Cell. Biol., February 1, 1999; 19(2): 1002 - 1015. [Abstract] [Full Text] [PDF]

				S. A. Onate, V. Boonyaratanakornkit, T. E. Spencer, S. Y. Tsai, M.-J. Tsai, D. P. Edwards, and B. W. O'Malley The Steroid Receptor Coactivator-1 Contains Multiple Receptor Interacting and Activation Domains That Cooperatively Enhance the Activation Function 1 (AF1) and AF2 Domains of Steroid Receptors J. Biol. Chem., May 15, 1998; 273(20): 12101 - 12108. [Abstract] [Full Text] [PDF]

				T. A. Knotts, R. S. Orkiszewski, R. G. Cook, D. P. Edwards, and N. L. Weigel Identification of a Phosphorylation Site in the Hinge Region of the Human Progesterone Receptor and Additional Amino-terminal Phosphorylation Sites J. Biol. Chem., March 9, 2001; 276(11): 8475 - 8483. [Abstract] [Full Text] [PDF]

				D. L. Bain, M. A. Franden, J. L. McManaman, G. S. Takimoto, and K. B. Horwitz The N-terminal Region of Human Progesterone B-receptors. BIOPHYSICAL AND BIOCHEMICAL COMPARISON TO A-RECEPTORS J. Biol. Chem., June 22, 2001; 276(26): 23825 - 23831. [Abstract] [Full Text] [PDF]