PMID- 26882544
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20210109
IS  - 1469-3178 (Electronic)
IS  - 1469-221X (Print)
IS  - 1469-221X (Linking)
VI  - 17
IP  - 3
DP  - 2016 Mar
TI  - Response to interferons and antibacterial innate immunity in the absence of 
      tyrosine-phosphorylated STAT1.
PG  - 367-82
LID - 10.15252/embr.201540726 [doi]
AB  - Signal transducer and activator of transcription 1 (STAT1) plays a pivotal role 
      in the innate immune system by directing the transcriptional response to 
      interferons (IFNs). STAT1 is activated by Janus kinase (JAK)-mediated 
      phosphorylation of Y701. To determine whether STAT1 contributes to cellular 
      responses without this phosphorylation event, we generated mice with Y701 mutated 
      to a phenylalanine (Stat1(Y701F)). We show that heterozygous mice do not exhibit 
      a dominant-negative phenotype. Homozygous Stat1(Y701F) mice show a profound 
      reduction in Stat1 expression, highlighting an important role for basal 
      IFN-dependent signaling. The rapid transcriptional response to type I IFN (IFN-I) 
      and type II IFN (IFNgamma) was absent in Stat1(Y701F) cells. Intriguingly, STAT1Y701F 
      suppresses the delayed expression of IFN-I-stimulated genes (ISG) observed in 
      Stat1(-/-) cells, mediated by the STAT2/IRF9 complex. Thus, Stat1(Y701F) 
      macrophages are more susceptible to Legionella pneumophila infection than 
      Stat1(-/-) macrophages. Listeria monocytogenes grew less robustly in Stat1(Y701F) 
      macrophages and mice compared to Stat1(-/-) counterparts, but STAT1Y701F is not 
      sufficient to rescue the animals. Our studies are consistent with a potential 
      contribution of Y701-unphosphorylated STAT1 to innate antibacterial immunity.
CI  - (c) 2016 The Authors. Published under the terms of the CC BY 4.0 license.
FAU - Majoros, Andrea
AU  - Majoros A
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
FAU - Platanitis, Ekaterini
AU  - Platanitis E
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
FAU - Szappanos, Daniel
AU  - Szappanos D
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna, Austria.
FAU - Cheon, HyeonJoo
AU  - Cheon H
AD  - Department of Molecular Genetics and Proteomics Core, Lerner Research Institute 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Vogl, Claus
AU  - Vogl C
AD  - Institute of Animal Breeding and Genetics, University of Veterinary Medicine 
      Vienna, Vienna, Austria.
FAU - Shukla, Priyank
AU  - Shukla P
AD  - Institute of Animal Breeding and Genetics, University of Veterinary Medicine 
      Vienna, Vienna, Austria.
FAU - Stark, George R
AU  - Stark GR
AD  - Department of Molecular Genetics and Proteomics Core, Lerner Research Institute 
      Cleveland Clinic, Cleveland, OH, USA.
FAU - Sexl, Veronika
AU  - Sexl V
AD  - Department for Biomedical Sciences, Institute of Pharmacology and Toxicology 
      University of Veterinary Medicine Vienna, Vienna, Austria.
FAU - Schreiber, Robert
AU  - Schreiber R
AD  - Department of Pathology and Immunology, Washington University School of Medicine, 
      St Louis, MO, USA.
FAU - Schindler, Christian
AU  - Schindler C
AD  - Departments of Microbiology & Immunology and Medicine, Columbia University, New 
      York, NY, USA.
FAU - Muller, Mathias
AU  - Muller M
AD  - Institute of Animal Breeding and Genetics, University of Veterinary Medicine 
      Vienna, Vienna, Austria.
FAU - Decker, Thomas
AU  - Decker T
AD  - Max F. Perutz Laboratories, University of Vienna, Vienna, Austria 
      thomas.decker@univie.ac.at.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160212
PL  - England
TA  - EMBO Rep
JT  - EMBO reports
JID - 100963049
RN  - 0 (IRF9 protein, mouse)
RN  - 0 (Interferon-Stimulated Gene Factor 3, gamma Subunit)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (STAT2 Transcription Factor)
RN  - 0 (Stat1 protein, mouse)
RN  - 0 (Stat2 protein, mouse)
RN  - 9008-11-1 (Interferons)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cells, Cultured
MH  - *Immunity, Innate
MH  - Interferon-Stimulated Gene Factor 3, gamma Subunit/metabolism
MH  - Interferons/*metabolism
MH  - Legionnaires' Disease/*immunology
MH  - Listeriosis/*immunology
MH  - Macrophages/immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mutation, Missense
MH  - Phosphorylation
MH  - *Protein Processing, Post-Translational
MH  - STAT1 Transcription Factor/*deficiency/genetics/metabolism
MH  - STAT2 Transcription Factor/metabolism
MH  - Second Messenger Systems
PMC - PMC4772975
OTO - NOTNLM
OT  - STAT1
OT  - innate immunity
OT  - interferon
OT  - pathogen
OT  - phosphorylation
EDAT- 2016/02/18 06:00
MHDA- 2016/12/15 06:00
PMCR- 2017/03/01
CRDT- 2016/02/17 06:00
PHST- 2015/05/22 00:00 [received]
PHST- 2016/01/13 00:00 [accepted]
PHST- 2016/02/17 06:00 [entrez]
PHST- 2016/02/18 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2017/03/01 00:00 [pmc-release]
AID - embr.201540726 [pii]
AID - EMBR201540726 [pii]
AID - 10.15252/embr.201540726 [doi]
PST - ppublish
SO  - EMBO Rep. 2016 Mar;17(3):367-82. doi: 10.15252/embr.201540726. Epub 2016 Feb 12.