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Reverse Yeast Two-hybrid System to Identify Mammalian Nuclear Receptor Residues that Interact with Ligands and/or Antagonists
Published on: November 15, 2013
Receptor to nucleus signaling via tyrosine phosphorylation of the p91 transcription factor
1Department of Pathology, State University of New York, Stony Brook, NY 11794, USA.
Abstract:
Recent studies on signal transduction stimulated by interferons have defined pathways that link cell surface receptors to target genes in the nucleus. After interferon binding, nonreceptor tyrosine kinases are activated that phosphorylate components of latent DNA-binding factors in the cytoplasm. These phosphorylated factors form multimeric complexes that translocate to the nucleus and bind to specific DNA sequences in the promoters of induced genes. A 91-kD factor (p91 or Stat 91) is activated by interferons and serves as a subunit partner in the composition of diverse transcription factors.
Insights
Interferon signaling activates latent DNA-binding factors, including p91 (Stat 91), which then move to the nucleus to regulate gene expression. This pathway is crucial for cellular responses to interferons.
Area of Science:
- Molecular Biology
- Immunology
- Cellular Signaling
Background:
- Interferons (IFNs) are critical cytokines involved in immune responses.
- Signal transduction pathways link cell surface receptors to nuclear gene regulation.
- Understanding IFN-stimulated pathways is key to deciphering cellular defense mechanisms.
Purpose of the Study:
- To elucidate the molecular mechanisms of interferon-stimulated signal transduction.
- To identify key factors involved in linking IFN receptors to target gene activation.
- To characterize the role of specific transcription factors in IFN-mediated gene expression.
Main Methods:
- Analysis of signal transduction pathways.
- Identification of activated protein kinases.
- Characterization of latent DNA-binding factors and their nuclear translocation.
- Investigation of transcription factor complex formation and DNA binding.
Main Results:
- Interferon binding activates nonreceptor tyrosine kinases.
- These kinases phosphorylate latent DNA-binding factors in the cytoplasm.
- Phosphorylated factors form complexes that translocate to the nucleus.
- A 91-kD factor (p91 or Stat 91) is activated and functions as a transcription factor subunit.
Conclusions:
- Interferon signaling involves a cascade of protein phosphorylations and translocations.
- The p91 (Stat 91) factor plays a significant role in mediating interferon's effects on gene expression.
- This pathway highlights the intricate regulation of gene transcription by extracellular signals.
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