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Science 11 December 1992:
Vol. 258. no. 5089, pp. 1808 - 1812
DOI: 10.1126/science.1281555
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Articles

Science, Vol 258, Issue 5089, 1808-1812
Copyright © 1992 by American Association for the Advancement of Science

articles

Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein

K Shuai, C Schindler, VR Prezioso, and JE Darnell Jr

Rockefeller University, New York, NY 10021.

Interferon-gamma (IFN-gamma) induces the transcription of the gene encoding a guanylate binding protein by activating a latent cytoplasmic factor, GAF (gamma-activated factor). GAF is translocated to the nucleus and binds a DNA element, the gamma-activated site. Through cross-linking and the use of specific antibodies GAF was found to be a 91-kilodalton DNA binding protein that was previously identified as one of four proteins in interferon-stimulated gene factor-3 (ISGF-3), a transcription complex activated by IFN-alpha. The IFN-gamma-dependent activation of the 91-kilodalton DNA binding protein required cytoplasmic phosphorylation of the protein on tyrosine. The 113-kilodalton ISGF-3 protein that is phosphorylated in response to IFN-alpha was not phosphorylated nor translocated to the nucleus in response to IFN-gamma. Thus the two different ligands result in tyrosine phosphorylation of different combinations of latent cytoplasmic transcription factors that then act at different DNA binding sites.


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L. J. Briggs, D. Stein, J. Goltz, V. C. Corrigan, A. Efthymiadis, S. Hubner, and D. A. Jans (1998)
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J. Tang, J. D. Gary, S. Clarke, and H. R. Herschman (1998)
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H. Kodama, K. Fukuda, J. Pan, S. Makino, M. Sano, T. Takahashi, S. Hori, and S. Ogawa (1998)
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Targeted Inhibition of Interferon-gamma -dependent Intercellular Adhesion Molecule-1 (ICAM-1) Expression Using Dominant-Negative Stat1.
M. J. Walter, D. C. Look, R. M. Tidwell, W. T. Roswit, and M. J. Holtzman (1997)
J. Biol. Chem. 272, 28582-28589
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Down-regulation of interferon gamma -activated STAT1 by UV light.
Y. Aragane, D. Kulms, T. A. Luger, and T. Schwarz (1997)
PNAS 94, 11490-11495
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Molecular Cloning of a New Interferon-induced PML Nuclear Body-associated Protein.
C. Gongora, G. David, L. Pintard, C. Tissot, T. D. Hua, A. Dejean, and N. Mechti (1997)
J. Biol. Chem. 272, 19457-19463
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Identification and Localization of a Skeletal Muscle Secrotonin 5-HT2A Receptor Coupled to the Jak/STAT Pathway.
I. Guillet-Deniau, A.-F. Burnol, and J. Girard (1997)
J. Biol. Chem. 272, 14825-14829
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