Advertisement

Membrane Glucocorticoid Receptors and Glucocorticoid Signal Transduction

  • Bahiru Gametchu
  • Cheryl S. Watson

Abstract

Membrane forms of some steroid hormone receptors (mSRs) were first reported almost three decades ago [(1, 2, 3),and references therein, but only recently have their identities and functions received intense focus by a growing number of laboratories. As a result, relatively little is known about the mSRs’ biochemical characteristics, molecular structure, protein targeting pathways, and the specific nature of their residence in the plasma membrane. Work conducted in our laboratory over the last 15 years, in several murine and human lymphoid cell lines, described a membrane form of the “nuclear” glucocorticoid receptor (mGR) whose level of expression is more strongly correlated with glucocorticoid (GC)-evoked lymphocytosis than is the intracellular GR (iGR) (4, 5, 6, 7, 8, 9, 10, 11, 12). This suggests that the GC-evoked signaling associated with apoptosis in lymphoid cells is initiated by a necessary mGR, and portends a great clinical importance for its measurement and manipulation in the treatment of lymphoproliferative diseases. Our studies began by demonstrating the existence of mGRs and capturing a population of cells enriched in the mGR, to perform correlative functional studies. We then more closely defined the characteristics of the mGR protein and established connections between mGR and the initiation of specific signaling cascades that terminate in apoptosis.

Keywords

Acute Lymphocytic Leukemia Glucocorticoid Receptor Triamcinolone Acetonide Spotted Seatrout Upstream Open Reading Frame 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Szego CM 1994 Cytostructural correlates of hormone action: new common ground in receptor-mediated signal propagation for steroid and peptide agonists. Endocrine 2:1079–1093Google Scholar
  2. 2.
    Watson CS, Gametchu B 1999 Membrane-initiated steroid actions and the proteins which mediate them [Review]. Proc Soc Exp Biol Med 220:9–19PubMedCrossRefGoogle Scholar
  3. 3.
    Makara GB, Haller J 2001 Non-genomic effects of glucocorticoids in the neural system - Evidence, mechanisms and implications. Progress in Neurobiology 65:367–390PubMedCrossRefGoogle Scholar
  4. 4.
    Gametchu B, Watson CS, Shih CY 1994 An S-49 cell line containing a smaller size glucocorticoid receptor is depleted of membrane-associated receptor and deficient in the lymphocytolytic response. Endocrine 2:429–437Google Scholar
  5. 5.
    Gametchu B, Chen F, Watson CS 1995 Intracellular and plasma membrane-resident glucocorticoid receptors in rodent leukemia models. In: Gametchu B (ed) Glucocorticoid Receptor Structure and Leukemic Cell Responses.R.G. Landes Co., Austin,75–103Google Scholar
  6. 6.
    Gametchu B, Watson CS 1995 Plasma membrane-associated glucocorticoid hormone receptor in human leukemic patients: Clinical implications. In: Gametchu B (ed) Glucocorticoid Receptor Structure and Leukemic Cell Responses.R.G. Landes Company, Austin, 163–176Google Scholar
  7. 7.
    Gametchu B 1987 Glucocorticoid receptor-like antigen in lymphoma cell membranes: Correlation to cell lysis. Science 236:456–461PubMedCrossRefGoogle Scholar
  8. 8.
    Gametchu B, Watson CS, Pasko D 1991 Size and steroid binding characterization of a membrane- associated glucocorticoid receptor in S-49 lymphoma cells. Steroids 56:402–410PubMedCrossRefGoogle Scholar
  9. 9.
    Gametchu B, Watson C, Shih C, Dashew B 1991 Studies on the arrangement of glucocorticoid receptors in the plasma membrane of S-49 lymphoma cells. Steroids 56:411–419PubMedCrossRefGoogle Scholar
  10. 10.
    Chen F, Watson CS, Gametchu B 1999 Multiple glucocorticoid receptor transcripts in membrane glucocorticoid receptor-enriched S-49 mouse leukemic cells. J Cell Biochem 74:418–429PubMedCrossRefGoogle Scholar
  11. 11.
    Sackey FNA, Watson CS, Gametchu B 1997 Cell cycle regulation of membrane glucocorticoid receptor in CCRF-CEM human ALL cells - correlation to apoptosis. American Journal of Physiology - Endocrinology & Metabolism 36:E571-E583Google Scholar
  12. 12.
    Chen F, Watson CS, Gametchu B 1999 Association of the glucocorticoid receptor alternatively-spliced transcript 1A with the presence of the high molecular weight membrane glucocorticoid receptor in mouse leukemic cells. J Cell Biochem 74:430–446PubMedCrossRefGoogle Scholar
  13. 13.
    Gametchu B, Watson CS, Wu S 1993 Use of receptor antibodies to demonstrate membrane glucocorticoid receptor in cells from human leukemic patients. FASEB J 7:1283–1293PubMedGoogle Scholar
  14. 14.
    Powell CE, Watson CS, Gametchu B 1999 Immunoaffinity isolation of native membrane glucocorticoid receptors from S-49 mGR++ cells: Biochemical characterization and interactions with hps 70 and 90. Endocrine 10:271–280PubMedCrossRefGoogle Scholar
  15. 15.
    Cheng XG, Hart GW 2000 Glycosylation of the murine estrogen receptor-alpha. Journal of Steroid Biochemistry & Molecular Biology 75:147–158CrossRefGoogle Scholar
  16. 16.
    Leclercq G 2002 Molecular forms of the estrogen receptor in breast cancer. Journal of Steroid Biochemistry and Molecular Biology 80:259–272PubMedCrossRefGoogle Scholar
  17. 17.
    Patino R, Thomas P 1990 Characterization of membrane receptor activity for 17a,20b,21-trihydroxy-4-pregnen-3-one in ovaries of spotted seatrout(Cynoscion nebulosus). General & Comparative Endocrinology 78:204–217CrossRefGoogle Scholar
  18. 18.
    Yoon K, Pellaroni L, Ramamoorthy K, Gaido K, Safe S 2000 Ligand structure-dependent differences in activation of estrogen receptor alpha in human HepG2 liver and U2 osteogenic cancer cell lines. Mol Cell Endocrinol 162:211–220PubMedCrossRefGoogle Scholar
  19. 19.
    Gametchu B, Chen F, Sackey FNA, Powell C, Watson CS 1999 Plasma membrane-resident glucocorticoid receptors in rodent lymphoma an human leukemia models. Steroids 64:107–119PubMedCrossRefGoogle Scholar
  20. 20.
    Gametchu B, Watson CS. Correlation of membrane glucocorticoid receptor levels with glucocorticoid-induced apoptotic competence using mutant leukemic and lymphoma cells lines. Journal of Cellular Biochemistry. 2002. In PressGoogle Scholar
  21. 21.
    Kuiper GGJM, Enmark E, Peltohuikko M, Nilsson S, Gustafsson J-Ä 1996 Cloning of a novel estrogen receptor expressed in rat prostate and ovary. Proc Natl Acad Sci USA 93:5925–5930PubMedCrossRefGoogle Scholar
  22. 22.
    Hawkins MB, Thornton JW, Crews D, Skipper JK, Dotte A, Thomas P 2000 Identification of a third distinct estrogen receptor and reclassification of estrogen receptors in teleosts. Proc Natl Acad Sci U S A 97:10751–10756PubMedCrossRefGoogle Scholar
  23. 23.
    Gearing KL, Cairns W, Okret S, Gustafsson J-Ä 1993 Heterogeneity in the 5’ untranslated region of the rat glucocorticoid receptor mRNA. J Steroid Biochem & Mol Biol 46:635–639CrossRefGoogle Scholar
  24. 24.
    Strähle U, Schmidt A, Kelsey G, Stewart AF, Cole TJ, Schmid W, Schütz G 1992 At least three promoters direct expression of the mouse glucocorticoid receptor gene. Proc Natl Acad Sci USA 89:6731–6735PubMedCrossRefGoogle Scholar
  25. 25.
    Morris DR 1997 Cis-acting mRNA structures in gene-specific translational control. In: Morris DR (ed) mRNA Metabolism and Post-Transcriptional Gene Regulation. Wiley-Liss, Inc., 165–180Google Scholar
  26. 26.
    Zimmer A, Zimmer AM, Reynolds K 1994 Tissue specific expression of the retinoic acid receptor-beta 2: regulation by short open reading frames in the 5’-noncoding region. J Cell Biol 127:1111–1119PubMedCrossRefGoogle Scholar
  27. 27.
    Mizokami A, Chang CS 1994 Induction of Translation by the 5’-Untranslated Region of Human Androgen Receptor Messenger-RNA. J Biol Chem 269:25655–25659PubMedGoogle Scholar
  28. 28.
    Diba F, Watson CS, Gametchu B 2001 5’UTR sequences of the glucocorticoid receptor 1A transcript encode a peptide associated with translational regulation of the glucocorticoid receptor. Journal of Cellular Biochemistry 81:149–161PubMedCrossRefGoogle Scholar
  29. 29.
    Reynolds K, Zimmer AM, Zimmer A 1996 Regulation of RAR beta 2 mRNA expression: evidence for an inhibitory peptide encoded in the 5’-untranslated region. J Cell Biol 134:827–835PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Bahiru Gametchu
    • 1
  • Cheryl S. Watson
    • 2
  1. 1.Department of PediatricsMedical College of WisconsinMilwaukeeUSA
  2. 2.Human Biological Chemistry & Genetics Dept.University of Texas Medical BranchGalvestonUSA

Personalised recommendations