Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2

Qiaozhu Su, Shuo Wang, Dionissios Baltzis, Li Ke Qu, Jennifer F. Raven, Suiyang Li, Andrew Hoi Tao Wong, Antonis E. Koromilas

Research output: Contribution to journalArticle

27 Citations (Scopus)

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 eIF2α 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 eIF2α phosphorylation.

Original languageEnglish (US)
Pages (from-to)265-270
Number of pages6
JournalEMBO Reports
Volume8
Issue number3
DOIs
StatePublished - Mar 1 2007

Fingerprint

Eukaryotic Initiation Factor-2
Phosphorylation
Interferons
Tyrosine
Phosphotransferases
Chemical activation
eIF-2 Kinase
Double-Stranded RNA
Cell Communication
Proteins
Cells
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2. / Su, Qiaozhu; Wang, Shuo; Baltzis, Dionissios; Qu, Li Ke; Raven, Jennifer F.; Li, Suiyang; Wong, Andrew Hoi Tao; Koromilas, Antonis E.

In: EMBO Reports, Vol. 8, No. 3, 01.03.2007, p. 265-270.

Research output: Contribution to journalArticle

Su, Q, Wang, S, Baltzis, D, Qu, LK, Raven, JF, Li, S, Wong, AHT & Koromilas, AE 2007, 'Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2', EMBO Reports, vol. 8, no. 3, pp. 265-270. https://doi.org/10.1038/sj.embor.7400891
Su, Qiaozhu ; Wang, Shuo ; Baltzis, Dionissios ; Qu, Li Ke ; Raven, Jennifer F. ; Li, Suiyang ; Wong, Andrew Hoi Tao ; Koromilas, Antonis E. / Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2. In: EMBO Reports. 2007 ; Vol. 8, No. 3. pp. 265-270.
@article{c0bebf957e80434b8d16af70184b685a,
title = "Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2",
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 eIF2α 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 eIF2α phosphorylation.",
author = "Qiaozhu Su and Shuo Wang and Dionissios Baltzis and Qu, {Li Ke} and Raven, {Jennifer F.} and Suiyang Li and Wong, {Andrew Hoi Tao} and Koromilas, {Antonis E.}",
year = "2007",
month = "3",
day = "1",
doi = "10.1038/sj.embor.7400891",
language = "English (US)",
volume = "8",
pages = "265--270",
journal = "EMBO Reports",
issn = "1469-221X",
publisher = "Nature Publishing Group",
number = "3",

}

TY - JOUR

T1 - Interferons induce tyrosine phosphorylation of the eIF2α kinase PKR through activation of Jak1 and Tyk2

AU - Su, Qiaozhu

AU - Wang, Shuo

AU - Baltzis, Dionissios

AU - Qu, Li Ke

AU - Raven, Jennifer F.

AU - Li, Suiyang

AU - Wong, Andrew Hoi Tao

AU - Koromilas, Antonis E.

PY - 2007/3/1

Y1 - 2007/3/1

N2 - 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 eIF2α 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 eIF2α phosphorylation.

AB - 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 eIF2α 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 eIF2α phosphorylation.

UR - http://www.scopus.com/inward/record.url?scp=33847349804&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33847349804&partnerID=8YFLogxK

U2 - 10.1038/sj.embor.7400891

DO - 10.1038/sj.embor.7400891

M3 - Article

VL - 8

SP - 265

EP - 270

JO - EMBO Reports

JF - EMBO Reports

SN - 1469-221X

IS - 3

ER -