STAT2 phosphorylation and signaling - PubMed (original) (raw)
Review
. 2013 Oct 1;2(4):e25790.
doi: 10.4161/jkst.25790. Epub 2013 Aug 12.
Affiliations
- PMID: 24416652
- PMCID: PMC3876438
- DOI: 10.4161/jkst.25790
Review
STAT2 phosphorylation and signaling
Håkan C Steen et al. JAKSTAT. 2013.
Abstract
STAT2 is an essential transcription factor in type I IFN mediated anti-viral and anti-proliferative signaling. STAT2 function is regulated by tyrosine phosphorylation, which is the trigger for STAT-dimerization, subsequent nuclear translocation, and transcriptional activation of IFN stimulated genes. Evidence of additional STAT2 phosphorylation sites has emerged as well as novel roles for STAT2 separate from the classical ISGF3-signaling. This review aims to summarize knowledge of phosphorylation-mediated STAT2-regulation and future avenues of related STAT2 research.
Keywords: STAT2; interferon; phosphorylation; receptors; regulation.
Figures
Figure 1. Schematic of the domain architecture of STAT2 and location of identified phosphorylation sites. ND, N-terminal domain; CCD, coiled-coil domain; DBD, DNA-binding domain; LD, linker domain; SH2, Src homology 2 domain; TAD, transactivation domain.
Figure 2. Illustration of type I interferon (IFN) signaling and ISGF3-mediated gene induction. Type I IFN binds IFNAR1 and IFNAR2 leading to transactivation of receptor-associated JAK kinases (JAK1 and TYK2). Several tyrosine residues on the intracellular chains of the receptor subunits are phosphorylated by JAKs, leading to recruitment and phosphorylation of STAT2 and STAT1. STAT2, STAT1, and IRF9 form the ISGF3 complex, which translocates to the nucleus by binding to importin-α5. In the nucleus, ISGF3 binds to the interferon-stimulated response element (ISRE) of interferon-stimulated genes (ISGs) and induce gene transcription with the help of additional co-activators recruited by STAT2.
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