Open AccessSTAT protein complexes activated by interferon-γ and gp 130 signaling molecules differ in their sequence preferences and trascriptional induction properties
Author(s) -
Peter Lamb,
H. Martin Seidel,
Jennifer A. Haslam,
Lawrence H. Milocco,
Linda Kessler,
Robert B. Stein,
Jon Rosen
Publication year - 1995
Publication title -
nucleic acids research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 9.008
H-Index - 537
eISSN - 1362-4954
pISSN - 0305-1048
DOI - 10.1093/nar/23.16.3283
Subject(s) - biology , stat1 , stat , stat protein , stat3 , cytokine , transcription factor , signal transduction , transcription (linguistics) , cytokine receptor , microbiology and biotechnology , receptor , genetics , gene , linguistics , philosophy
Activation of members of the STAT (signal transducers and activators of transcription) family of latent transcription factors is an early event following the binding of many cytokines to their cognate receptors. Although the patterns of STATs activated by different cytokines are well described, the consequences of differential STAT activation are less well studied. We show by mutational analysis that STAT binding elements (SBEs) exist that discriminate between STAT complexes containing STAT1 alpha, STAT3 or both, and that these elements show altered cytokine responsiveness. We also show that in the context of a minimal promoter, single and multiple SBEs exhibit strikingly different patterns of transcriptional activation in response to IFN-gamma, IL-6, OSM or LIF. These differences in transcriptional activation are correlated with the differential ability of these cytokines to activate STAT1 alpha, STAT3 or both. Our results show that the pattern of STATs activated by a cytokine and the arrangement and sequence of the SBEs in the responding promoter have a profound effect on the ability of the cytokine to elicit a transcriptional response.