The DOI matches its Crossref record; 63 of the 63 references it cites were found in a registry or an index.
Signal Integration via PKR
Abstract
The vital role of interferons (IFNs) as mediators of innate immunity is well established. It has recently become apparent that one of the pivotal proteins in mediating the antiviral activity of IFNs, the double-stranded RNA (dsRNA)-activated protein kinase (PKR), also functions as a signal transducer in the proinflammatory response to different agents. PKR is a member of a small family of kinases that are activated by extracellular stresses and that phosphorylate the α subunit of protein synthesis initiation factor eIF-2, thereby inhibiting protein synthesis. The activation of PKR during infection by viral dsRNA intermediates results in the inhibition of viral replication. PKR also mediates the activation of signal transduction pathways by proinflammatory stimuli, including bacterial lipopolysaccharide (LPS), tumor necrosis factor α (TNF-α), and interleukin 1 (IL-1). PKR is a component of the inhibitor of κB (IκB) kinase complex and plays either a catalytic or structural role in the activation of IκB kinase, depending on the stimulus. The activities of the stress-activated protein kinases p38 and c-Jun NH 2 -terminal kinase (JNK) are also regulated by PKR in a pathway that leads to the production of proinflammatory cytokines. This review will focus on the role of PKR in nuclear factor κ B (NF-κB) and mitogen-activated protein kinase (MAPK) pathways, because these have been the subjects of a series of publications over the past year that have reported conflicting findings. Although the conflicts may not be resolved in this review, suggestions are made for experiments that could lead to a clearer understanding of the mechanisms involved.
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1 retracted
RETRACTED: DNA-PKcs Is Required for Activation of Innate Immunity by Immunostimulatory DNA
Chu, W.-M., Gong, X., Li, Z.-W., Takabayashi, K., Ouyang, H.-H., Chen, Y., Lois, A., Chen, D. J., Li, G. C., Karin, M., et al. (2000) · Cell · doi:10.1016/s0092-8674(00)00194-x · Cited by 178
RetractedA Toll-like receptor recognizes bacterial DNA
Hemmi, H., Takeuchi, O., Kawai, T., Kaisho, T., Sato, S., Sanjo, H., Matsumoto, M., Hoshino, K., Wagner, H., Takeda, K., et al. (2000) · Nature · doi:10.1038/35047123 · Cited by 6,491 · cited 1×
“” This was confirmed by the recent discovery that the pattern recognition receptor TLR9, and components of its signaling pathway, mediate cellular responses to CpG DNA (57).”
BackgroundRegulated Translation Initiation Controls Stress-Induced Gene Expression in Mammalian Cells
Harding, H. P., Novoa, I., Zhang, Y., Zeng, H., Wek, R., Schapira, M., & Ron, D. (2000) · Molecular Cell · doi:10.1016/s1097-2765(00)00108-8 · Cited by 3,276
Kaufman, R. J. (1999) · Genes & Development · doi:10.1101/gad.13.10.1211 · Cited by 2,248
A cytokine-responsive IκB kinase that activates the transcription factor NF-κB
DiDonato, J. A., Hayakawa, M., Rothwarf, D. M., Zandi, E., & Karin, M. (1997) · Nature · doi:10.1038/41493 · Cited by 2,125
IKK-1 and IKK-2: Cytokine-Activated IκB Kinases Essential for NF-κB Activation
Mercurio, F., Zhu, H., Murray, B. W., Shevchenko, A., Bennett, B. L., Li, J. W., Young, D. B., Barbosa, M., Mann, M., Manning, A., et al. (1997) · Science · doi:10.1126/science.278.5339.860 · Cited by 2,040
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Self-citationZandi, E., Rothwarf, D. M., Delhase, M., Hayakawa, M., & Karin, M. (1997) · Cell · doi:10.1016/s0092-8674(00)80406-7 · Cited by 1,812
Meurs, E., Chong, K., Galabru, J., Thomas, N. S. B., Kerr, I. M., Williams, B. R. G., & Hovanessian, A. G. (1990) · Cell · doi:10.1016/0092-8674(90)90374-n · Cited by 1,017
Self-citationPositive and Negative Regulation of IκB Kinase Activity Through IKKβ Subunit Phosphorylation
Delhase, M., Hayakawa, M., Chen, Y., & Karin, M. (1999) · Science · doi:10.1126/science.284.5412.309 · Cited by 852
Cited by
Cell Type-Specific Involvement of RIG-I in Antiviral Response
Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.010 · Cited by 1,368
Interferons at age 50: past, current and future impact on biomedicine
Borden, E. C., Sen, G. C., Uze, G., Silverman, R. H., Ransohoff, R. M., Foster, G. R., & Stark, G. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2422 · Cited by 1,154
Deoxynivalenol: mechanisms of action, human exposure, and toxicological relevance
Pestka, J. J. (2010) · Archives of Toxicology · doi:10.1007/s00204-010-0579-8 · Cited by 1,015
Impact of Protein Kinase PKR in Cell Biology: from Antiviral to Antiproliferative Action
García, M. A., Gil, J., Ventoso, I., Guerra, S., Domingo, E., Rivas, C., & Esteban, M. (2006) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00027-06 · Cited by 818
The dsRNA protein kinase PKR: Virus and cell control
García, M. A., Meurs, E. F., & Esteban, M. (2007) · Biochimie · doi:10.1016/j.biochi.2007.03.001 · Cited by 644
Metadata
- Authors
- Williams, B. R. G.
- Venue
- Science's STKE
- Published
- 2001-07-03
- Volume
- 2001
- Issue
- 89
- Pages
- re2-re2
- ISSN
- 1525-8882 (ISSN-L)
- OpenAlex
- W2090603241
- Cited by
- 406
- References
- 63
- FWCI
- 6.36
- Type
- journal article
- Language
- en
- Open access
- closed
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