Phosphorylation of eukaryotic translation initiation factor 2 mediates apoptosis in response to activation of the double-stranded RNA-dependent protein kinase.

The Journal of Biological Chemistry
S P SrivastavaR J Kaufman

Abstract

The interferon-inducible, double-stranded (ds) RNA-dependent serine/threonine protein kinase (PKR) plays a role in viral pathogenesis, cell growth, and differentiation and is implicated as a tumor suppressor gene. Expression of a trans-dominant negative, catalytically inactive mutant PKR protected NIH3T3 cells from apoptosis in response to either treatment with tumor necrosis factor alpha (TNF alpha), serum deprivation. In cells expressing mutant PKR, TNF alpha, but not dsRNA induced transcription from a nuclear factor kappa B-dependent promoter, demonstrating specificity for dsRNA in signaling through the PKR pathway. Serum or platelet-derived growth factor addition to serum-deprived mutant PKR-expressing cells induced transcription of the early response genes c-fos and c-jun, indicating that the immediate early response signaling was intact. Overexpression of wild-type PKR in a transient DNA transfection system was sufficient to induce apoptosis. TNF alpha-induced apoptosis correlated with increased phosphorylation of the alpha subunit of eukaryotic translation initiation factor 2 (eIF-2 alpha), the primary physiological substrate of the PKR. Furthermore, forced expression of a nonphosphorylatable S51A mutant eIF-2 alpha part...Continue Reading

References

Mar 1, 1992·Proceedings of the National Academy of Sciences of the United States of America·N D PerkinsG J Nabel
Jan 1, 1991·Annual Review of Biochemistry·J W Hershey
Jan 1, 1990·Methods in Enzymology·R J Kaufman
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·R PetryshynI M London
Sep 1, 1980·Proceedings of the National Academy of Sciences of the United States of America·P S Thomas
May 24, 1994·Proceedings of the National Academy of Sciences of the United States of America·H ParkS Venkatesan
Aug 2, 1994·Proceedings of the National Academy of Sciences of the United States of America·T ItoW S May
Mar 10, 1995·Science·S Nagata, P Golstein
Jan 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·E F MeursA G Hovanessian
Jul 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·P Lengyel
Feb 1, 1995·Current Opinion in Genetics & Development·Y Shen, T E Shenk
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A KumarB R Williams
Oct 21, 1994·Cell·Z N Oltvai, S J Korsmeyer
May 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·T E DeverA G Hinnebusch
Feb 11, 1994·Science·V GagliardiniJ Yuan
Apr 1, 1993·Genes & Development·M Debbas, E White
Mar 15, 1996·European Journal of Biochemistry·V M Pain
Nov 1, 1996·Science·D J Van AntwerpI M Verma
Oct 29, 1996·Proceedings of the National Academy of Sciences of the United States of America·M C YeungA S Lau
Jan 7, 1997·Proceedings of the National Academy of Sciences of the United States of America·M W MelvilleM G Katze

❮ Previous
Next ❯

Citations

Nov 15, 2002·Biotechnology and Bioengineering·Renata E Cudna, Alan J Dickson
Jan 26, 2012·Inflammatory Bowel Diseases·Stewart Siyan CaoRandal J Kaufman
May 8, 2003·Journal of Biosciences·Seyed E HasnainM Krishnaveni
Feb 16, 2005·Apoptosis : an International Journal on Programmed Cell Death·M S IordanovB E Magun
Feb 18, 2010·Apoptosis : an International Journal on Programmed Cell Death·Iyer AartiKolluru V A Ramaiah
Dec 18, 2007·Cellular and Molecular Neurobiology·Marianna Pap, József Szeberényi
Sep 14, 2013·Trends in Biochemical Sciences·Nancy KedershaPaul Anderson
Oct 31, 2000·Journal of the Neurological Sciences·B C WhiteG S Krause
May 9, 2000·Mechanisms of Ageing and Development·W LadigesM Gale
Nov 28, 2002·Pharmacology & Therapeutics·Bent H Havsteen
Dec 26, 2001·Experimental Hematology·S FagerlieG C Bagby
Jul 16, 2003·Cancer Letters·Jean M NussbaumShobha Gunnery
Apr 28, 1999·Trends in Microbiology·H Everett, G McFadden
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·R JagusG N Barber
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·O SavinovaR Jagus
Jan 7, 2006·Cell Death and Differentiation·B He
Aug 5, 1999·The Biochemical Journal·S SatohK Shimotohno
Mar 26, 2002·Journal of Veterinary Medicine. B, Infectious Diseases and Veterinary Public Health·S Essbauer, W Ahne
Jan 4, 2007·The Journal of Biological Chemistry·Kenneth W Adams, Geoffrey M Cooper
Jul 16, 2003·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Michael J Clemens
Aug 5, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S L Tan, M G Katze
Aug 5, 1999·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M Pavón, M Esteban
Oct 22, 1998·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S L Tan, M G Katze
Sep 17, 2004·Molecular Biology of the Cell·Natalie GilksPaul Anderson
Jul 19, 2000·The EMBO Journal·L B MaggiJ A Corbett
Oct 3, 2002·The EMBO Journal·Frédéric IseniDaniel Kolakofsky
Aug 30, 2008·Journal of the National Cancer Institute·Daniela TrisciuoglioGiovanni Melillo
Jul 21, 2006·Nucleic Acids Research·Eyal KamhiJoseph Sperling

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis