The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
Double-Stranded RNA-Dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis
Open accessAbstract
SUMMARY As chronic inflammation is a hallmark of obesity, pathways that integrate nutrient and pathogen sensing pathways are of great interest in understanding the mechanisms of insulin resistance, type 2 diabetes, and other chronic metabolic pathologies. Here, we provide evidence that double-stranded RNA dependent protein kinase (PKR) can respond to nutrient signals as well as endoplasmic reticulum (ER) stress and coordinate the activity of other critical inflammatory kinases such as the c-Jun N-terminal kinase (JNK) to regulate insulin action and metabolism. PKR also directly targets and modifies insulin receptor substrate and hence integrates nutrients and insulin action with a defined pathogen response system. Dietary and genetic obesity features marked activation of PKR in adipose and liver tissues and absence of PKR alleviates metabolic deterioration due to nutrient or energy excess in mice. These findings demonstrate PKR as a critical component of an inflammatory complex that responds to nutrients and organelle dysfunction.
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Cites
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
TLR4 links innate immunity and fatty acid-induced insulin resistance
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006) · Journal of Clinical Investigation · doi:10.1172/jci28898 · Cited by 3,690
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Self-citationNutrient sensing and inflammation in metabolic diseases
Hotamisligil, G. S., & Erbay, E. (2008) · Nature Reviews Immunology · doi:10.1038/nri2449 · Cited by 1,040
PKC-θ knockout mice are protected from fat-induced insulin resistance
Kim, J. K., Fillmore, J. J., Sunshine, M. J., Albrecht, B., Higashimori, T., Kim, D.-W., Liu, Z.-X., Soos, T. J., Cline, G. W., O’Brien, W. R., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci200422230 · Cited by 500
Endoplasmic reticulum stress is reduced in tissues of obese subjects after weight loss
Gregor, M. F., Yang, L., Fabbrini, E., Mohammed, B. S., Eagon, J. C., Hotamisligil, G. S., & Klein, S. (2009) · Diabetes · doi:10.2337/db08-1220 · Cited by 488 · cited 1×
“In both mouse and human, there is a consistent and marked increase in phosphorylation of eIF2a and JNK activity in obese metabolic tissues (Gregor et al., 2009).”
Background
Cited by
Inflammatory Mechanisms in Obesity
Gregor, M. F., & Hotamisligil, G. S. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101322 · Cited by 3,754
Autophagy and the Integrated Stress Response
Kroemer, G., Mariño, G., & Levine, B. (2010) · Molecular Cell · doi:10.1016/j.molcel.2010.09.023 · Cited by 3,506
Autophagy in immunity and inflammation
Levine, B., Mizushima, N., & Virgin, H. W. (2011) · Nature · doi:10.1038/nature09782 · Cited by 3,289
Endoplasmic reticulum stress and the inflammatory basis of metabolic disease
Hotamisligil, G. S. (2010) · Cell · doi:10.1016/j.cell.2010.02.034 · Cited by 2,802
Self-citationHuman nutrition, the gut microbiome and the immune system
Kau, A. L., Ahern, P. P., Griffin, N. W., Goodman, A. L., & Gordon, J. I. (2011) · Nature · doi:10.1038/nature10213 · Cited by 2,588
Metadata
- Authors
- Nakamura, T., Furuhashi, M., Li, P., Cao, H., Tuncman, G., Sonenberg, N., Gorgun, C. Z., & Hotamisligil, G. S.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 140
- Issue
- 3
- Pages
- 338-348
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2111793830
- Cited by
- 505
- References
- 6
- FWCI
- 33.34
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Nakamura, T., Furuhashi, M., Li, P., Cao, H., Tuncman, G., Sonenberg, N., Gorgun, C. Z., & Hotamisligil, G. S. (2010). Double-Stranded RNA-Dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell. https://doi.org/10.1016/j.cell.2010.01.001
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