Imperial College London
Portrait Picture

DrTeresaThurston

Faculty of Medicine, Department of Infectious Disease

Senior Lecturer in Molecular Microbiology
 
 
 
//

Contact

 

+44 (0)20 7594 3072t.thurston

 
 
//

Location

 

2.40Flowers buildingSouth Kensington Campus

//

Summary

 

Publications

Citation

BibTex format

@article{Panagi:2020:10.1016/j.chom.2019.11.002,
author = {Panagi, I and Jennings, E and Zeng, J and Günster, RA and Stones, CD and Mak, H and Jin, E and Stapels, DAC and Subari, NZ and Pham, THM and Brewer, SM and Ong, SYQ and Monack, DM and Helaine, S and Thurston, TLM},
doi = {10.1016/j.chom.2019.11.002},
journal = {Cell Host and Microbe},
pages = {41--53.e6},
title = {Salmonella effector SteE converts the mammalian serine/threonine kinase GSK3 into a tyrosine kinase to direct macrophage polarization.},
url = {http://dx.doi.org/10.1016/j.chom.2019.11.002},
volume = {27},
year = {2020}
}
Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Many Gram-negative bacterial pathogens antagonize anti-bacterial immunity through translocated effector proteins that inhibit pro-inflammatory signaling. In addition, the intracellular pathogen Salmonella enterica serovar Typhimurium initiates an anti-inflammatory transcriptional response in macrophages through its effector protein SteE. However, the target(s) and molecular mechanism of SteE remain unknown. Here, we demonstrate that SteE converts both the amino acid and substrate specificity of the host pleiotropic serine/threonine kinase GSK3. SteE itself is a substrate of GSK3, and phosphorylation of SteE is required for its activity. Remarkably, phosphorylated SteE then forces GSK3 to phosphorylate the non-canonical substrate signal transducer and activator of transcription 3 (STAT3) on tyrosine-705. This results in STAT3 activation, which along with GSK3 is required for SteE-mediated upregulation of the anti-inflammatory M2 macrophage marker interleukin-4Rα (IL-4Rα). Overall, the conversion of GSK3 to a tyrosine-directed kinase represents a tightly regulated event that enables a bacterial virulence protein to reprogram innate immune signaling and establish an anti-inflammatory environment.
AU  - Panagi,I
AU  - Jennings,E
AU  - Zeng,J
AU  - Günster,RA
AU  - Stones,CD
AU  - Mak,H
AU  - Jin,E
AU  - Stapels,DAC
AU  - Subari,NZ
AU  - Pham,THM
AU  - Brewer,SM
AU  - Ong,SYQ
AU  - Monack,DM
AU  - Helaine,S
AU  - Thurston,TLM
DO  - 10.1016/j.chom.2019.11.002
EP  - 53
PY  - 2020///
SN  - 1931-3128
SP  - 41
TI  - Salmonella effector SteE converts the mammalian serine/threonine kinase GSK3 into a tyrosine kinase to direct macrophage polarization.
T2  - Cell Host and Microbe
UR  - http://dx.doi.org/10.1016/j.chom.2019.11.002
UR  - https://www.ncbi.nlm.nih.gov/pubmed/31862381
UR  - https://www.sciencedirect.com/science/article/pii/S1931312819305840?via%3Dihub
UR  - http://hdl.handle.net/10044/1/76008
VL  - 27
ER  -
Download