This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Thomas, M. J. Articles by Rotwein, P. Search for Related Content PubMed PubMed Citation Articles by Thomas, M. J. Articles by Rotwein, P.

 Previous Article  |  Next Article 

Mol. Cell. Biol., Jan 1995, 12-18, Vol 15, No. 1
Copyright © 1995, American Society for Microbiology

Growth hormone rapidly activates rat serine protease inhibitor 2.1 gene transcription and induces a DNA-binding activity distinct from those of Stat1, -3, and -4

MJ Thomas, AM Gronowski, SA Berry, PL Bergad and P Rotwein
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.

Transcriptional regulation by growth hormone (GH) represents the culmination of signal transduction pathways that are initiated by the cell surface GH receptor and are targeted to the nucleus. Recent studies have demonstrated that the activated GH receptor can stimulate Stat1, a cytoplasmic transcription factor that becomes tyrosine phosphorylated and translocates to the nucleus, where it can interact with specific DNA sequences to modulate gene expression. GH also has been found to induce protein binding to a portion of the rat serine protease inhibitor (Spi) 2.1 gene promoter that is required for GH- induced transcription of Spi 2.1. Using GH-deficient hypophysectomized rats as a model, we show that GH treatment rapidly and potently induces both nuclear Spi 2.1 mRNA expression in the liver and specific nuclear protein binding to a 45-bp segment of the Spi 2.1 gene promoter. A GH- inducible gel-shifted complex appears within 15 min of systemic hormone administration and can be inhibited by an antiphosphotyrosine monoclonal antibody but is not blocked by a polyclonal antiserum to Stat1, Stat3, or Stat4, even though the nucleotide sequence contains two gamma interferon-activated sequence-like elements that could interact with STAT proteins. By Southwestern (DNA-protein) blot analysis, approximately 41- and 35-kDa GH-inducible proteins were detected in hepatic nuclear extracts with the Spi 2.1 DNA probe. Thus, a GH-activated signaling pathway stimulates Spi 2.1 gene expression through a unique mechanism that does not appear to involve known members of the STAT family of transcription factors.

This article has been cited by other articles:

• Fang, P., Kofoed, E. M., Little, B. M., Wang, X., Ross, R. J. M., Frank, S. J., Hwa, V., Rosenfeld, R. G. (2006). A Mutant Signal Transducer and Activator of Transcription 5b, Associated with Growth Hormone Insensitivity and Insulin-Like Growth Factor-I Deficiency, Cannot Function as a Signal Transducer or Transcription Factor. J. Clin. Endocrinol. Metab. 91: 1526-1534 [Abstract] [Full Text]  
• Wang, W., Wang, L., Endoh, A., Hummelke, G., Hawks, C. L, Hornsby, P. J (2005). Identification of {alpha}-enolase as a nuclear DNA-binding protein in the zona fasciculata but not the zona reticularis of the human adrenal cortex. J Endocrinol 184: 85-94 [Abstract] [Full Text]  
• Woelfle, J., Rotwein, P. (2004). In vivo regulation of growth hormone-stimulated gene transcription by STAT5b. Am. J. Physiol. Endocrinol. Metab. 286: E393-E401 [Abstract] [Full Text]  
• Woelfle, J., Billiard, J., Rotwein, P. (2003). Acute Control of Insulin-like Growth Factor-I Gene Transcription by Growth Hormone through Stat5b. J. Biol. Chem. 278: 22696-22702 [Abstract] [Full Text]  
• Bergad, P. L., Schwarzenberg, S. J., Humbert, J. T., Morrison, M., Amarasinghe, S., Towle, H. C., Berry, S. A. (2000). Inhibition of growth hormone action in models of inflammation. Am. J. Physiol. Cell Physiol. 279: C1906-C1917 [Abstract] [Full Text]  
• Le Stunff, C., Rotwein, P. (1998). Growth Hormone Stimulates Interferon Regulatory Factor-1 Gene Expression in the Liver. Endocrinology 139: 859-866 [Abstract] [Full Text]  
• Freeth, J. S., Silva, C. M., Whatmore, A. J., Clayton, P. E. (1998). Activation of the Signal Transducers and Activators of Transcription Signaling Pathway by Growth Hormone (GH) in Skin Fibroblasts from Normal and GH Binding Protein-Positive Laron Syndrome Children. Endocrinology 139: 20-28 [Abstract] [Full Text]  
• Umayahara, Y., Ji, C., Centrella, M., Rotwein, P., McCarthy, T. L. (1997). CCAAT/Enhancer-binding Protein delta  Activates Insulin-like Growth Factor-I Gene Transcription in Osteoblasts. IDENTIFICATION OF A NOVEL CYCLIC AMP SIGNALING PATHWAY IN BONE. J. Biol. Chem. 272: 31793-31800 [Abstract] [Full Text]  
• Strous, G. J., van Kerkhof, P., Govers, R., Rotwein, P., Schwartz, A. L. (1997). Growth Hormone-induced Signal Transduction Depends on an Intact Ubiquitin System. J. Biol. Chem. 272: 40-43 [Abstract] [Full Text]  
• Kordula, T., Ripperger, J., Morella, K. K., Travis, J., Baumann, H. (1996). Two Separate Signal Transducer and Activator of Transcription Proteins Regulate Transcription of the Serine Proteinase Inhibitor-3 Gene in Hepatic Cells. J. Biol. Chem. 271: 6752-6757 [Abstract] [Full Text]  
• Han, Y., Leaman, D. W., Watling, D., Rogers, N. C., Groner, B., Kerr, I. M., Wood, W. I., Stark, G. R. (1996). Participation of JAK and STAT Proteins in Growth Hormone-induced Signaling. J. Biol. Chem. 271: 5947-5952 [Abstract] [Full Text]  
• Bergad, P. L., Shih, H.-M., Towle, H. C., Schwarzenberg, S. J., Berry, S. A. (1995). Growth Hormone Induction of Hepatic Serine Protease Inhibitor 2.1 Transcription Is Mediated by a Stat5-related Factor Binding Synergistically to Two [IMAGE]-Activated Sites. J. Biol. Chem. 270: 24903-24910 [Abstract] [Full Text]