Volume 16, No 1, Jan 2006
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 16 Issue 1, January 2006: 113-123
ORIGINAL ARTICLES
Modulation of the activation of Stat1 by the interferon-gamma receptor complex
Christopher D Krause1, Wen He1, Sergei Kotenko2, Sidney Pestka1, 3, 4
1Department of Molecular Genetics, Microbiology and Immunology, Robert Wood Johnson Medical School -The University of Medicine and Dentistry of New Jersey, 675 Hoes Lane West, Piscataway, NJ 08855, USA;
2Department of Biochemistry & Molecular Biology, New Jersey Medical School - The University of Medicine and Dentistry of New Jersey, 185 South Orange Avenue, Newark, NJ 07101, USA;
3Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, New Jersey 08903-2681, USA;
4PBL Biomedical Laboratories, 131 Ethel Road West, Suite 6, Piscataway, NJ 08854-5900, USA
Correspondence: Sidney Pestka(pestka@umdnj.edu)
The activation of Stat1 by the interferon-gamma (IFN-γ) receptor complex is responsible for the transcription of a significant portion of IFN-γ induced genes. Many of these genes are responsible for the induction of an apoptotic state in response to IFN-γ. In the absence of Stat1 activation, IFN-γ instead induces a proliferative response. Modifying Stat1 activation by IFN-γ may have pharmacological benefits. We report that the rate of activation of Stat1 can be altered in HeLa cells by overexpressing either the IFN-γR1 chain or the IFN-γR2 chain. These alterations occur in hematopoietic cell lines: Raji cells and monocytic cell lines, which have average and above-average IFN-γR2 surface expression, activate Stat1 similarly to HeLa cells and HeLa cells overexpressing IFNγR2, respectively. The rapid Stat1 activation seen in HeLa cells can be inhibited by overexpressing a chimeric IFN-γR2 chain that does not bind Jak2 or (when high concentrations of IFN-γ are used) by overexpressing IFN-γR1. These data are consistent with a model in which the recruitment of additional Jak2 activity to a signaling complex accelerates the rate of Stat1 activation. We conclude that the rate of activation of Stat1 in cells by IFN-γ can be modified by regulating either receptor chain and speculate that pharmacological agents which modify receptor chain expression may alter IFN-γ receptor signal transduction.
Cell Research (2006) 16:113-123 . doi:10.1038/sj.cr.7310015; published online 16 January 2006
FULL TEXT | PDF
Browse 1772
