PMID: 7545299Aug 29, 1995Paper

The interferon-inducible double-stranded RNA-activated protein kinase self-associates in vitro and in vivo

Proceedings of the National Academy of Sciences of the United States of America
R C PatelG C Sen

Abstract

The interferon-inducible double-stranded (ds) RNA-activated protein kinase (PKR) exhibits antiviral, anticellular, and antitumor activities. The mechanisms of its enzymatic activation by autophosphorylation and of the observed transdominant inhibitory phenotype of enzymatically inactive mutants have invoked PKR dimerization. Here we present direct evidence in support of PKR-PKR interaction. We show that radiolabeled PKR can specifically interact with matrix-bound unlabeled PKR in the absence of dsRNA. The self-association activity resides, in part, in the N-terminal region of 170 residues, which also constitutes the dsRNA-binding domain (DRBD). DRBD can bind to matrix-bound PKR or to matrix-bound DRBD. Dimerization of DRBD was directly demonstrated by chemical crosslinking. Affinity chromatography and electrophoretic mobility supershift assays demonstrated that mutants that fail to bind dsRNA can still exhibit protein-protein interaction. The PKR-PKR interaction could also be observed in a two-hybrid transcriptional activation assay in mammalian cells and consequently is likely to be an important feature of PKR activity in vivo.

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·G S FengB R Williams
Dec 1, 1992·Genes & Development·S R Green, M B Mathews
Aug 1, 1990·Proceedings of the National Academy of Sciences of the United States of America·T G LeeM G Katze
Sep 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·M L ZappM R Green
Jan 1, 1991·Annual Review of Biochemistry·J W Hershey
Nov 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·F Imani, B L Jacobs
Dec 1, 1989·Journal of Interferon Research·A G Hovanessian
Sep 15, 1987·European Journal of Biochemistry·A G Hovanessian, J Galabru
Jul 1, 1970·Proceedings of the National Academy of Sciences of the United States of America·G E Davies, G R Stark
Feb 17, 1995·The Journal of Biological Chemistry·S Y DesaiB Thimmapaya
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
Jul 5, 1994·Proceedings of the National Academy of Sciences of the United States of America·A KumarB R Williams
Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·S B LeeM Esteban
Nov 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·A M TakacsA K Banerjee

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Citations

Jan 1, 1996·Biochimie·H D Robertson, M B Mathews
Apr 27, 1999·The International Journal of Biochemistry & Cell Biology·R JagusG N Barber
Jul 8, 2009·Biochemistry·Gregory A PetersGanes C Sen
Apr 28, 2000·European Journal of Biochemistry·J L Harcourt, M K Offermann
Oct 10, 1995·Proceedings of the National Academy of Sciences of the United States of America·G P CosentinoN Sonenberg
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 23, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·M J Clemens, A Elia
Oct 23, 1997·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·S Y Desai, G C Sen
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 29, 2004·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Zan XuBryan R G Williams
Apr 10, 2010·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Anthony J Sadler
Aug 4, 1998·The EMBO Journal·R C Patel, G C Sen
Jan 15, 1997·Nucleic Acids Research·D Y Jin, K T Jeang
Oct 18, 2002·Nucleic Acids Research·Katsumi KasashimaHiroshi Sakamoto
Dec 22, 2007·Nucleic Acids Research·Megan MittelstadtRekha C Patel
Sep 22, 2006·Journal of Virology·Morgan HakkiAdam P Geballe
Mar 10, 2001·Molecular and Cellular Biology·G A PetersG C Sen
Jun 6, 2000·Microbiology and Molecular Biology Reviews : MMBR·M GaleM G Katze
Sep 27, 2000·Cell Stress & Chaperones·C X Yuan, W B Gurley
Aug 24, 2013·International Journal of Molecular Sciences·Kiyoshi MasudaIssei Imoto
Aug 5, 1998·Proceedings of the National Academy of Sciences of the United States of America·D W LeamanG R Stark
Apr 28, 2006·FEBS Letters·Rogerio MargisPeter M Waterhouse
Oct 7, 2014·Microbes and Infection·Lívia Harumi YamashiroAndré Báfica
Nov 15, 2008·Journal of Molecular Biology·Madhurima SinghRekha C Patel
Nov 28, 2006·Gene·Stephen FascianoRekha C Patel
Apr 5, 2012·Journal of Cellular Biochemistry·Madhurima Singh, Rekha C Patel

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