Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog

Thomas E. Dever, Rajaraman Sripriya, Jeanne R. Mclachlin, Jingfang Lu, John R. Fabian, Scot Kimball, Lois K. Miller

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

Phosphorylation of eukaryotic translation initiation factor 2α (eIF2a) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA- regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.

Original languageEnglish (US)
Pages (from-to)4164-4169
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number8
DOIs
StatePublished - Apr 14 1998

Fingerprint

Eukaryotic Initiation Factor-2
Eukaryotic Initiation Factors
Phosphotransferases
Protein Kinases
Phosphorylation
RNA
Baculoviridae
Insects
Yeasts
Viruses
Proteins

All Science Journal Classification (ASJC) codes

  • General

Cite this

Dever, Thomas E. ; Sripriya, Rajaraman ; Mclachlin, Jeanne R. ; Lu, Jingfang ; Fabian, John R. ; Kimball, Scot ; Miller, Lois K. / Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog. In: Proceedings of the National Academy of Sciences of the United States of America. 1998 ; Vol. 95, No. 8. pp. 4164-4169.
@article{9340cf98ce254aca8450dcd2d9697ce1,
title = "Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog",
abstract = "Phosphorylation of eukaryotic translation initiation factor 2α (eIF2a) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA- regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.",
author = "Dever, {Thomas E.} and Rajaraman Sripriya and Mclachlin, {Jeanne R.} and Jingfang Lu and Fabian, {John R.} and Scot Kimball and Miller, {Lois K.}",
year = "1998",
month = "4",
day = "14",
doi = "10.1073/pnas.95.8.4164",
language = "English (US)",
volume = "95",
pages = "4164--4169",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog. / Dever, Thomas E.; Sripriya, Rajaraman; Mclachlin, Jeanne R.; Lu, Jingfang; Fabian, John R.; Kimball, Scot; Miller, Lois K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 95, No. 8, 14.04.1998, p. 4164-4169.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Disruption of cellular translational control by a viral truncated eukaryotic translation initiation factor 2α kinase homolog

AU - Dever, Thomas E.

AU - Sripriya, Rajaraman

AU - Mclachlin, Jeanne R.

AU - Lu, Jingfang

AU - Fabian, John R.

AU - Kimball, Scot

AU - Miller, Lois K.

PY - 1998/4/14

Y1 - 1998/4/14

N2 - Phosphorylation of eukaryotic translation initiation factor 2α (eIF2a) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA- regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.

AB - Phosphorylation of eukaryotic translation initiation factor 2α (eIF2a) is a common cellular mechanism to limit protein synthesis in stress conditions. Baculovirus PK2, which resembles the C-terminal half of a protein kinase domain, was found to inhibit both human and yeast eIF2α kinases. Insect cells infected with wild-type, but not pk2-deleted, baculovirus exhibited reduced eIF2α phosphorylation and increased translational activity. The negative regulatory effect of human protein kinase RNA- regulated (PKR), an eIF2α kinase, on virus production was counteracted by PK2, indicating that baculoviruses have evolved a unique strategy for disrupting a host stress response. PK2 was found in complex with PKR and blocked kinase autophosphorylation in vivo, suggesting a mechanism of kinase inhibition mediated by interaction between truncated and intact kinase domains.

UR - http://www.scopus.com/inward/record.url?scp=0032516048&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032516048&partnerID=8YFLogxK

U2 - 10.1073/pnas.95.8.4164

DO - 10.1073/pnas.95.8.4164

M3 - Article

C2 - 9539707

AN - SCOPUS:0032516048

VL - 95

SP - 4164

EP - 4169

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -