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PMID: 17290288 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Interferons induce tyrosine phosphorylation of the eIF2alpha kinase PKR through activation of Jak1 and Tyk2.

EMBO reports ·Vol. 8 ·No. 3 ·2007-03-00 ·Pages 265-70

Su Q, Wang S, Baltzis D, Qu LK, Raven JF, Li S, Wong AH, Koromilas AE

Abstract

The interferon (IFN)-inducible, double-stranded RNA activated protein kinase (PKR) is a dual-specificity kinase, which has an essential role in the regulation of protein synthesis by phosphorylating the translation eukaryotic initiation factor 2 (eIF2). Here, we show the tyrosine (Tyr) phosphorylation of PKR in response to type I or type II IFNs. We show that PKR physically interacts with either Jak1 or Tyk2 in unstimulated cells and that these interactions are increased in IFN-treated cells. We also show that PKR acts as a substrate of activated Jaks, and is phosphorylated at Tyr 101 and Tyr 293 both in vitro and in vivo. Moreover, we provide strong evidence that both the induction of eIF2alpha phosphorylation and inhibition of protein synthesis by IFN are impaired in cells lacking Jak1 or Tyk2, which corresponds to a lack of induction of PKR tyrosine phosphorylation. We conclude that PKR tyrosine phosphorylation provides an important link between IFN signalling and translational control through the regulation of eIF2alpha phosphorylation.

MeSH Terms
Animals Cell Line Electrophoresis, Polyacrylamide Gel Gene Expression Regulation/physiology Immunoblotting Interferons/metabolism Janus Kinase 1/metabolism Mice Phosphorylation Signal Transduction/physiology TYK2 Kinase/metabolism Tyrosine/metabolism eIF-2 Kinase/metabolism
Chemicals
Tyrosine Interferons Jak1 protein, mouse Janus Kinase 1 TYK2 Kinase Tyk2 protein, mouse eIF-2 Kinase
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Su Qiaozhu
Lady Davis Institute, Sir Mortimer B. Davis-Jewish General Hospital, 3999 Cote Ste-Catherine Road, Montreal, Quebec, Canada.
Wang Shuo
Baltzis Dionissios
Qu Li-Ke
Raven Jennifer F
Li Suiyang
Wong Andrew Hoi-Tao
Koromilas Antonis E
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Article Info
Journal
EMBO reports
Abbr.
EMBO Rep
ISSN
1469-221X
DOI
10.1038/sj.embor.7400891
Published
2007-03-00
Epub
2007-00-09
Pages
265-70
Language
English
Region
England
NLM ID
100963049
PMCID
PMC1808029
Subset
IM
External Links
PubMed source DOI: 10.1038/sj.embor.7400891 PMC Full Text View journal details
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