Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase
Joint Authors
Johnson, Howard M.
Ahmed, Chulbul M.
Noon-Song, Ezra
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-05-28
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
A small group of only seven transcription factors known as STATs (signal transducer and activator of transcription) are considered to be canonical determinants of specific gene activation for a plethora of ligand/receptor systems.
The activation of STATs involves a family of four tyrosine kinases called JAK kinases.
JAK1 and JAK2 activate STAT1 in the cytoplasm at the heterodimeric gamma interferon (IFNγ) receptor, while JAK1 and TYK2 activate STAT1 and STAT2 at the type I IFN heterodimeric receptor.
The same STATs and JAKs are also involved in signaling by functionally different cytokines, growth factors, and hormones.
Related to this, IFNγ-activated STAT1 binds to the IFNγ-activated sequence (GAS) element, but so do other STATs that are not involved in IFNγ signaling.
Activated JAKs such as JAK2 and TYK2 are also involved in the epigenetics of nucleosome unwrapping for exposure of DNA to transcription.
Furthermore, activated JAKs and STATs appear to function coordinately for specific gene activation.
These complex events have not been addressed in canonical STAT signaling.
Additionally, the function of noncoding enhancer RNAs, including their role in enhancer/promoter interaction is not addressed in the canonical STAT signaling model.
In this perspective, we show that JAK/STAT signaling, involving membrane receptors, is essentially a variation of cytoplasmic nuclear receptor signaling.
Focusing on IFN signaling, we showed that ligand, IFN receptor, the JAKs, and the STATs all undergo endocytosis and ATP-dependent nuclear translocation to promoters of genes specifically activated by IFNs.
We argue here that the vacuolar ATPase (V-ATPase) proton pump probably plays a key role in endosomal membrane crossing by IFNs for receptor cytoplasmic binding.
Signaling of nuclear receptors such as those of estrogen and dihydrotestosterone provides templates for making sense of the specificity of gene activation by closely related cytokines, which has implications for lymphocyte phenotypes.
American Psychological Association (APA)
Johnson, Howard M.& Noon-Song, Ezra& Ahmed, Chulbul M.. 2019. Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1192856
Modern Language Association (MLA)
Johnson, Howard M.…[et al.]. Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase. Mediators of Inflammation No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1192856
American Medical Association (AMA)
Johnson, Howard M.& Noon-Song, Ezra& Ahmed, Chulbul M.. Noncanonical IFN Signaling, Steroids, and STATs: A Probable Role of V-ATPase. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1192856
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1192856