Distinct Phosphorylation of STAT1 Confers Distinct DNA Binding and Gene-regulatory Properties

Hozaifa Metwally ,Tadamitsu Kishimoto

doi:10.33696/signaling.1.012

Abstract

Signal transducer and activator of transcription 1 (STAT1) protein plays a pivotal role in various biological processes especially the regulation of innate and adaptive immune responses. Phosphorylation represents a key step in the activation of STAT1 and its transcriptional outcome.

Highlights

Signal transducer and activator of transcription (STAT) proteins have been recognized about three decades ago for their dual function as signal transducers and transcriptional activators [1,2,3]
The basic model for STAT proteins activation depends on binding of extracellular ligand resulting in active conformational change of the cytoplasmic domain of their specific receptors leading to the activation of various tyrosine kinases, which in turn phosphorylate a key tyrosine residue located at the region between the Src-homology 2 (SH2) and the transactivation domain (TAD) of STAT proteins resulting in STAT-STAT dimerization [10]
Type I and III IFNs activates JAK1/TYK2 kinase complex, which promotes tyrosine phosphorylation of both Signal transducer and activator of transcription 1 (STAT1) (Tyr701) and STAT2 (Tyr690) leading to their heterodimerization and association with IFN regulatory factor 9 (IRF9) forming the interferon stimulated genes (ISGs) factor 3 (ISGF3) complex that activates the transcription of multiple ISGs through binding to IFN-stimulated regulatory elements (ISREs) in their DNA promoter regions [21,22,23,24,25,26]

Summary

Introduction

Signal transducer and activator of transcription (STAT) proteins have been recognized about three decades ago for their dual function as signal transducers and transcriptional activators [1,2,3]. Type II IFN activates JAK1/ JAK2 kinase complex, which in turn promotes tyrosine phosphorylation at residue 701 (Tyr701) of STAT1, followed by its homodimerization, nuclear translocation and transcriptional activation of IFN-γ–induced genes through binding at gamma-activated sequence (GAS) of their DNA promoter regions [17,18,19,20].

Results

Conclusion