Publication Date:
1992-12-21
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Shuai, K -- Schindler, C -- Prezioso, V R -- Darnell, J E Jr -- New York, N.Y. -- Science. 1992 Dec 11;258(5089):1808-12.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Rockefeller University, New York, NY 10021.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/1281555" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Base Sequence
;
Binding Sites
;
Cell Line
;
Cell Nucleus/metabolism
;
DNA-Binding Proteins/isolation & purification/*metabolism
;
Electrophoresis, Gel, Two-Dimensional
;
Electrophoresis, Polyacrylamide Gel
;
GTP-Binding Proteins/*genetics
;
Gene Expression Regulation/drug effects
;
Interferon-alpha/pharmacology
;
Interferon-gamma/*pharmacology
;
Models, Biological
;
Molecular Sequence Data
;
Molecular Weight
;
Oligodeoxyribonucleotides
;
Phosphorylation
;
Phosphotyrosine
;
Promoter Regions, Genetic
;
STAT1 Transcription Factor
;
Signal Transduction/drug effects
;
*Trans-Activators
;
*Transcription, Genetic/drug effects
;
Tyrosine/analogs & derivatives/analysis
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics