Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids

Journal of Clinical Investigation

Volumn 111, Issue 11, 2003, Pages 1651-1664

  Kousteni, Stavroula ^a   Han, Li ^a   Chen, Jin Ran ^a   Almeida, Maria ^a   Plotkin, Lilian I ^a   Bellido, Teresita ^a   Manolagas, Stavros C ^a,b,c  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^b CENTRAL ARKANSAS VETERANS HEALTHCARE SYSTEM   (United States)

^c NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4 ESTREN 3ALPHA,17BETA DIOL; ANDROGEN RECEPTOR; ANDROSTANOLONE; CCAAT ENHANCER BINDING PROTEIN BETA; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; EARLY GROWTH RESPONSE FACTOR 1; ESTRADIOL; ESTRANE DERIVATIVE; ESTROGEN RECEPTOR; JANUS KINASE; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHOTRANSFERASE; PROTEIN C FOS; PROTEIN C JUN; PROTEIN SHC; PROTEIN TYROSINE KINASE; RALOXIFENE; SEX HORMONE; STEROID RECEPTOR; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR ELK 1; UNCLASSIFIED DRUG; 4 ESTREN 3,17 DIOL; 4-ESTREN-3,17-DIOL; ANTIESTROGEN; CCAAT ENHANCER BINDING PROTEIN ALPHA; DNA BINDING PROTEIN; ELK1 PROTEIN, HUMAN; ELK1 PROTEIN, MOUSE; LIGAND; ONCOPROTEIN; SELECTIVE ESTROGEN RECEPTOR MODULATOR;

ANIMAL CELL; ARTICLE; BINDING SITE; CONTROLLED STUDY; DOWN REGULATION; ENZYME PHOSPHORYLATION; GENE EXPRESSION REGULATION; GENE TARGETING; GENETIC TRANSCRIPTION; GENITAL SYSTEM; HUMAN; HUMAN CELL; LIGAND BINDING; MOUSE; NONHUMAN; OSTEOLYSIS; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RECEPTOR BINDING; REGULATORY MECHANISM; SEMINAL VESICLE; UTERUS; ANIMAL; BIOLOGICAL MODEL; BONE; CELL LINE; CYTOPLASM; DOSE RESPONSE; DRUG EFFECT; ENZYME ACTIVATION; GENETIC TRANSFECTION; HELA CELL; METABOLISM; OSTEOBLAST; PLASMID; PROTEIN TERTIARY STRUCTURE; REPORTER GENE; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; UPREGULATION; WESTERN BLOTTING;

ANIMALS; BLOTTING, WESTERN; BONE AND BONES; CCAAT-ENHANCER-BINDING PROTEIN-ALPHA; CELL LINE; CYTOPLASM; DNA-BINDING PROTEINS; DOSE-RESPONSE RELATIONSHIP, DRUG; DOWN-REGULATION; ENZYME ACTIVATION; ESTRENES; ESTROGEN ANTAGONISTS; ETS-DOMAIN PROTEIN ELK-1; GENES, REPORTER; HELA CELLS; HUMANS; LIGANDS; MICE; MODELS, BIOLOGICAL; OSTEOBLASTS; PHOSPHOTRANSFERASES; PLASMIDS; PROTEIN STRUCTURE, TERTIARY; PROTO-ONCOGENE PROTEINS; PROTO-ONCOGENE PROTEINS C-FOS; PROTO-ONCOGENE PROTEINS C-JUN; RALOXIFENE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; SELECTIVE ESTROGEN RECEPTOR MODULATORS; TRANSCRIPTION FACTORS; TRANSCRIPTION, GENETIC; TRANSFECTION; UP-REGULATION;

EID: 0038819062     PISSN: 00219738     EISSN: None     Source Type: Journal    
DOI: 10.1172/JCI200317261     Document Type: Article

References (78)

1. McKenna, N.J., and O'Malley, B.W. 2002. Combinatorial control of gene expression by nuclear receptors and coregulators. Cell 108:465-474.
2. Moggs, J.G., and Orphanides, G. 2001. Estrogen receptors: orchestrators of pleiotropic cellular responses. EMBO Rep. 2:775-781.
3. Hall, J.M., Couse, J.F., and Korach, K.S. 2001. The multifaceted mechanisms of estradiol and estrogen receptor signaling. J. Biol. Chem. 276:36869-36872.
4. McDonnell, D.P. 1999. The molecular pharmacology of SERMs. Trends Endocrinol. Metab. 10:301-311.
5. Falkenstein, E., Tillmann, H.C., Christ, M., Feuring, M., and Wehling, M. 2000. Multiple actions of steroid hormones - a focus on rapid, nongenomic effects, Pharmacol. Rev. 52:513-556.
6. Valverde, M.A., et al. 1999, Acute activation of Maxi-K channels (hSlo) by estradiol binding to the beta subunit. Science. 285:1929-1931.
7. Pietras, R.J., and Szego, C.M. 1977. Specific binding sites for oestrogen at the outer surfaces of isolated endometrial cells. Nature. 265:69-72.
8. Simoncini, T., et al. 2000. Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase. Nature 407:538-541.
9. Chang, L., and Karin, M. 2001. Mammalian MAP kinase signalling cascades. Nature. 410:37-40.
10. Kousteni, S., et al. 2001. Nongenotropic, sex-nonspecific signaling through the estrogen or androgen receptors: dissociation from transcriptional activity. Cell. 104:719-730.
11. Kousteni, S., et al. 2002. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science. 298:843-846.
12. Sun, J., et al. 1999. Novel ligands that function as selective estrogens or antiestrogens for estrogen receptor-α or estrogen receptor-beta;. Endocrinology. 140:800-804.
13. Stauffer, S.R., et al. 2000. Pyrazole ligands: structure-affinity/activity relationships and estrogen receptor-alpha-selective agonists. J. Med. Chem. 43:4934-4947.
14. Jilka, R.L., Weinstein, R.S., Bellido, T., Parfitt, A.M., and Manolagas, S.C. 1998. Osteoblast programmed cell death (apoptosis): modulation by growrh factors and cyrokines. J. Bone Miner. Res. 13:793-802.
15. Kato, Y., Windle, JJ., Koop, B.A., Mundy, G.R., and Bonewald, L.F. 1997. Establishment of an osreocyte-like cell line, MLO-Y4. J. Bone Miner. 12:2014-2023.
16. Lecka-Czernik, B, et al. 1999. Inhibition of Osf2/Cbfa1 expression and terminal osteoblast differentiation by PPARgamma2. J. Cell Biochem. 74:357-371.
17. Pottratz, S.T., Bellido, T., Mocharla, H., Crabb, D., and Manolagas, S.C. 1994. 17β-estradiol inhibits expression of human interleukin-6 promoter-reporter constructs by a receptor-dependent mechanism. J. Clin. Invest. 93:944-950.
18. Weinstein, R.S., et al. 2002. Promotion of osteoclast survival and antagonism of bisphosphonate-induced osteoclast apoptosis by glucocorticoids. J. Clin. Invest. 109:1041-1048. doi:10.1172/JCI200214538.
19. Duan, R., Xie, W., Burghatdt, R.C., and Safe, S. 2001. Estrogen receptor-mediated activation of the serum response element in MCF-7 cells through MAPK-dependent phosphorylation of Elk-1. J. Biol. Chem. 276:11590-11598.
20. Tian, J., and Karin, M. 1999. Stimulation of Elk1 transcriptional activity by mitogen-activated protein kinases is negatively regulated by protein phosphatase 2B (calcineurin). J. Biol. Chem. 274:15173-10180.
21. Zhang, Z., Baron, R., and Horne, W.C. 2000. Integrin engagement, the actin cytoskeleton, and c-Src are required for the induction by calcitonin of the tyrosine phosphorylation of paxillin and HEF1, but not for calcitonin-induced ERK1/2 phosphorylation. J. Biol. Chem. 275:37219-37223.
22. Walk, S.F., March, M.E., and Ravichandran, K.S. 1998. Roles of Lck, Syk and ZAP-70 tyrosine kinases in TCR-mediated phosphorylation of the adapter protein Shc. Eur. J. Immunol. 28:2265-2275.
23. Mansour, S.J., et al. 1994. Transformation of mammalian cells by constitutively, active MAP kinase kinase. Science. 265:966-970.
24. Whitmarsh, A.J., Shore, P., Sharrocks, A.D., and Davis, R.J. 1995. Integration of MAP kinase signal transduction pathways at the serum response element. Science, 269:403-407.
25. Datta, S.R., et al. 1997. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell. 91:231-241.
26. Zhou, X.M., Liu, Y., Payne, G., Lutz, R.J., and Chittenden, T. 2000. Growth factors inactivate the cell death promoter BAD by phosphorylation of its BH3 domain on Set155. J. Biol. Chem. 275:25046-25051.
27. Ahlbom, E., Grandison, L., Bonfoco, E., Zhivotovsky, B., and Ceccatelli, S. 1999. Androgen treatment of neonatal rats decreases susceptibility of cerebellar granule neurons to oxidative stress in vitro. Eur. J. Neurosci. 11:1285-1291.
28. Brown, P.H., Chen, T.K., and Birrer, M.J. 1994. Mechanism of action of a dominant-negative mutant of c-Jun. Oncogene. 9:791-799.
29. Kalderon, D., Roberts, B.L., Richardson, W.D., and Smith, A.E. 1984. A short amino acid sequence able to specify nuclear location. Cell. 39:499-509.
30. Rubinfeld, H., Hanoch, T., and Seger, R. 1999. Identification of a cytoplasmic-retention sequence in ERK2. J. Biol. Chem. 274:30349-30352.
31. Hill, C.S., and Treisman, R., 1995. Transcriptional regulation by extra-cellular signals: Mechanisms and specificity. Cell. 80:199-211.
32. Treisman, R. 1996. Regulation of transcription by MAP kinase cascades. Curr. Opin. Cell Biol. 8:205-215.
33. Minden, A., et al. 1994. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science. 266:1719-1723.
34. Paumelle, R., et al. 2000. Sequential activation of ERK and repression of JNK by scatter factor/heparocyte growth factor in Madin-Darby canine kidney epithelial cells. Mol. Biol. Cell. 11:3751-3763.
35. Su, B., and Karin, M. 1996. Mitogen-activated protein kinase cascades and regulation of gene expression. Curr. Opin. Immunol. 8:402-411.
36. Cruzalegui, F.H., Cano, E., and Treisman, R. 1999. ERK activation induces phosphorylation of Elk-1 at multiple S/T-P motifs to high stoichiometry. Oncogene. 18:7948-7957.
37. Bonni, A., et al. 1999. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and -independent mechanisms. Science. 286:1358-1362.
38. Buck, M., Poli, V., van der Geer, G.P., Chojkier, M., and Hunter, T. 1999. Phosphorylation of rat serine 105 or mouse threonine 217 in C/EBP beta is required for hepatocyte proliferation induced by TGF alpha. Mol. Cell. 4:1087-1092.
39. Marais, R., Wynne, J., and Treisman, R. 1993. The SRF accessory protein Elk-1 contains a growth factor-regulated transcriptional activation domain. Cell. 73:381-393.
40. de Jager, T., et al. 2001. Mechanisms of estrogen receptor action in the myocardium. Rapid gene activation via the ERK1/2 pathway and serum response elements. J. Biol. Chem. 276:27873-27880.
41. Song, R.X., et al. 2002. Linkage of rapid estrogen action to MAPK activation by ERalpha-Shc association and Shc pathway activation. Mol. Endocrinol. 16:116-127.
42. Scheid, M.P., and Duronio, V. 1998. Dissociation of cytokine-induced phosphorylation of Bad and activation of PKB/akt: involvement of MEK upstream of Bad phosphorylation. Proc. Natl. Acad. Sci. U. S. A. 95:7439-7444.
43. Yang, E., et al. 1995. Bad, a heterodimeric partner for Bcl-XL and Bcl-2, displaces Bax and promotes cell death. Cell. 80:285-291.
44. Scheid, M.P., Schubert, K.M., and Duronio, V. 1999. Regulation of bad phosphorylation and association with Bcl-x(L) by the MAPK/Erk kinase. J. Biol. Chem. 274:31108-31113.
45. Peruzzi, F., et al. 1999. Multiple signaling pathways of the insulin-like growth factor 1 receptor in protection from apoptosis. Mol. Cell. Biol. 19:7203-7215.
46. Lizcano, J.M., Morrice, N., and Cohen, P 2000. Regulation of BAD by cAMP-dependent protein kinase is mediated via phosphorylation of a novel site, Ser155. Biochem. J. 349:547-557.
47. Datta, S.R., Brunet, A., and Greenberg, M.E. 1999. Cellular survival: a play in three Akts. Genes Dev. 13:2905-2927.
48. Bryant, H.U., Glasebrook, A.L., Yang, N.N., and Sato, M. 1999. An estrogen receptor basis for raloxifene action in bone. J. Steroid Biochem. Mol. Biol. 69:37-44.
49. Erlandsson, M.C., Jonsson, C.A., Lindberg, M.K., Ohlsson, C., and Carlsten, H. 2002. Raloxifene- and estradiol-mediated effects on uterus, bone and B lymphocytes in mice. J. Endocrinol. 175:319-327.
50. Black, L.J., et al. 1994. Raloxifene (LY139481 HCI) prevents bone loss and reduces serum cholesterol without causing uterine hypertrophy in ovariectomized rats. J. Clin. Invest. 93:63-69.
51. Evans, G., Bryant, H.U., Magee, D., Sato, M., and Turner, R.T. 1994. The effects of raloxifene on tibia histomorphometry in ovariectomized rats. Endocrinology. 134:2283-2288.
52. Frolik, C.A., Bryant, H.U., Black, E.C., Magee, D.E., and Chandrasekhar, S. 1996. Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate. Bone. 18:621-627.
53. Sato, M., Kim, J., Short, L.L., Slemenda, C.W., and Bryant, H.U. 1995. Longitudinal and cross-sectional analysis of raloxifene effects on tibiae from ovariectomized aged rats. J. Pharmacol. Exp. Ther. 272:1252-1259.
54. 1996. Random House Unabridged Dictionary. 2nd edition. S.B. Flexner and L.C. Hauck, editors. Random House. New York, New York, USA. 2027 pp.
55. Chen, J.-R., et al. 2002. Interchangeable ligand/receptor interactions mediate ERK activation and the pro- and anti-apoptotic effects of estrogens and androgens on murine osteoclasts and osteoblasts from females and males: a molecular explanation of the in vivo equivalence of their skeletal actions in either sex. J. Bone Miner. Res. 17:S133. (Abstr.)
56. Kushner, P.J., et al. 2000. Estrogen receptor pathways to AP-1. J. Steroid Biochem. Mol. Biol. 74:311-317.
57. Boyden, L.M., et al. 2002. High bone density due to a mutation in LDL-receptor-related protein 5. N. Engl. J. Med. 346:1513-1521.
58. Grotewold, L., and Rüther, U. 2002. The Wnt antagonist Dickkopf-1 is regutaled by Bmp signaling and c-Jun and modulates programmed cell death. EMBO J. 21:966-975.
59. Manolagas, S.C., and Kousteni, S. 2001. Non-reproductive sites of action of reproductive hormones. Endocrinology. 142:2200-2204.
60. Khosla, S., et al. 1998. Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: A key role for bioavailable estrogen. J. Clin. Endocrin. Metab. 83:2266-2274.
61. Bilezikian, J.P., Morishima, A., Bell, J., and Grumbach, M.M. 1998. Increased bone mass as a result of estrogen therapy in a man with aromatase deficiency. N. Engl. J. Med. 339:599-603.
62. -/- mice. J. Clin. Invest. 107:333-340.
63. Hodgin, J.B., Knowles, J.W., Kim, H.S., Smithies, O., and Maeda, N. 2002. Interactions between endothelial nitric oxide synthase and sex hormones in vascular protection in mice. J. Clin. Invest. 109:541-548. doi:10.1172/JCI20214066.
64. Croniger, C.M., et al. 2001. Mice with a deletion in the gene for CCAAT/enhancer-binding protein beta have an attenuated response to cAMP and impaired carbohydrate metabolism. J. Biol. Chem. 276:629-638.
65. Lewis, D.A., Bracamonte, M.P., Rud, K.S., and Miller, V.M. 2001. Selected contribution: effects of sex and ovariectomy on responses to platelets in porcine femoral veins. J. Appl. Physiol. 91:2823-2830.
66. Vanderschueren, D., Boonen, S., and Bouillon, R. 1998. Action of androgens versus estrogens in male skeletal homeostasis. Bone. 23:391-394.
67. Manolagas, S.C., Kousteni, S., and Jilka, R.L. 2002. Sex steroids and bone. Recent Prog. Horm. Res. 57:385-409.
68. Komesaroff, P.A., et al. 2001. Low-dose estrogen supplementation improves vascular function in hypogonadal men. Hypertension. 38:1011-1016
69. Dupont, S., et al. 2000. Effect of single and compound knockouts of estrogen receptors alpha (ERalpha) and beta (ERbeta) on mouse reproductive phenotypes. Development. 127:4277-4291.
70. Gentile, M.A., Zhang, H., Harada, S., Rodan, G.A., and Kimmel, D.B. 2001. Bone response to estrogen replacement in ovx double estrogen receptor-(α and β) knockout mice. J. Bone Miner. Res. 16:S146. (Abstr.)
71. Lindberg, M.K., et al. 2002. Estrogen receptor specificity for the effects of estrogen in ovariectomized mice. J. Endocrinol. 174:167-178.
72. Sims, N.A., et al. 2003. A functional androgen receptor is non sufficient to allow estradiol to protect bone after gonadectomy in estradiol receptor-deficient mice. J. Clin. Invest. 111:1319-1327. doi:10.1172/JCI200317246.
73. Vandenput, L., et al. 2001 Testosterone prevents orchidectomy-induced bone loss in estrogen receptor-α knockout mice. Biochem. Biophys. Res Commun. 285:70-76.
74. Smith, E.P., et al. 1994. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N. Engl. J. Med. 331:1056-1061.
75. Bjarnason, N.H., et al. 2001. Six and twelve month changes in bone turnover are related to reduction in vertebral fracture risk during 3 years of raloxifene treatment in postmenopausal osteoporosis. Osteoporos. Int. 12:922-930.
76. Kousteni, S., et al. 2001. Nongenotropic activation of MAP kinases and prevention of apoptosis by SERMs in osteoblasts/osteocytes: a property shared by hydroxytamoxifene and idoxifene, but not raloxifene. J. Bone Miner. Res. 16:S415. (Abstr.)
77. Doran, P.M., Riggs, B.L., Atkinson, E.J., and Khosla, S. 2001 Effects of raloxifene, a selective estrogen receptor modulator, on bone turnover markers and serum sex steroid and lipid levels in elderly men. J. Bone Miner. Res. 16:2118-2125.
78. Ott, S.M, Oleksik, A., Lu, Y., Harper, K., and Lips, P. 2002. Bone histomorphometric and biochemical marker results of a 2-year placebo-controlled trial of raloxifene in postmenopausal women. J. Bone Miner. Res. 17:341-348.