Phosphorylation of STAT2 on serine-734 negatively regulates the IFN-α-induced antiviral response

15Citations
Citations of this article
23Readers
Mendeley users who have this article in their library.

Abstract

Serine phosphorylation of STAT proteins is an important posttranslational modification event that, in addition to tyrosine phosphorylation, is required for strong transcriptional activity. However, we recently showed that phosphorylation of STAT2 on S287 induced by type I interferons (IFN-α and IFN-β), evoked the opposite effect. S287-STAT2 phosphorylation inhibited the biological effects of IFN-α.We now report the identification and characterization of S734 on the C-terminal transactivation domain of STAT2 as a new phosphorylation site that can be induced by type I IFNs. IFN-α- induced S734-STAT2 phosphorylation displayed different kinetics to that of tyrosine phosphorylation. S734-STAT2 phosphorylation was dependent on STAT2 tyrosine phosphorylation and JAK1 kinase activity. Mutation of S734-STAT2 to alanine (S734A) enhanced IFN- a-driven antiviral responses compared to those driven by wild-type STAT2. Furthermore, DNA microarray analysis demonstrated that a small subset of type I IFN stimulated genes (ISGs) was induced more by IFNa in cells expressing S734A-STAT2 when compared to wildtype STAT2. Taken together, these studies identify phosphorylation of S734-STAT2 as a new regulatory mechanism that negatively controls the type I IFN-antiviral response by limiting the expression of a select subset of antiviral ISGs.

Cite

CITATION STYLE

APA

Steen, H. C., Kotredes, K. P., Nogusa, S., Harris, M. Y., Balachandran, S., & Gamero, A. M. (2016). Phosphorylation of STAT2 on serine-734 negatively regulates the IFN-α-induced antiviral response. Journal of Cell Science, 129(22), 4190–4199. https://doi.org/10.1242/jcs.185421

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free