The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
p38 MAPK–mediated regulation of Xbp1s is crucial for glucose homeostasis
Open accessAbstract
Here we show that p38 mitogen-activated protein kinase (p38 MAPK) phosphorylates the spliced form of X-box binding protein 1 (Xbp1s) on its Thr48 and Ser61 residues and greatly enhances its nuclear migration in mice, whereas mutation of either residue to alanine substantially reduces its nuclear translocation and activity. We also show that p38 MAPK activity is markedly reduced in the livers of obese mice compared with lean mice. Further, we show that activation of p38 MAPK by expression of constitutively active MAP kinase kinase 6 (MKK6Glu) greatly enhances nuclear translocation of Xbp1s, reduces endoplasmic reticulum stress and establishes euglycemia in severely obese and diabetic mice. Hence, our results define a crucial role for phosphorylation on Thr48 and Ser61 of Xbp1s in the maintenance of glucose homeostasis in obesity, and they suggest that p38 MAPK activation in the livers of obese mice could lead to a new therapeutic approach to the treatment of type 2 diabetes.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Inflammation and insulin resistance
Shoelson, S. E. (2006) · Journal of Clinical Investigation · doi:10.1172/jci29069 · Cited by 4,769
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
IKK-β links inflammation to obesity-induced insulin resistance
Arkan, M. C., Hevener, A. L., Greten, F. R., Maeda, S., Li, Z.-W., Long, J. M., Wynshaw-Boris, A., Poli, G., Olefsky, J., & Karin, M. (2005) · Nature Medicine · doi:10.1038/nm1185 · Cited by 1,773
Park, E. J., Lee, J. H., Yu, G.-Y., He, G., Ali, S. R., Holzer, R. G., Österreicher, C. H., Takahashi, H., & Karin, M. (2010) · Cell · doi:10.1016/j.cell.2009.12.052 · Cited by 1,764
Self-citationMitogen-Activated Protein Kinases: Specific Messages from Ubiquitous Messengers
Schaeffer, H. J., & Weber, M. J. (1999) · Molecular and Cellular Biology · doi:10.1128/mcb.19.4.2435 · Cited by 1,600 · cited 1×
“, and that anisomycin or TNF-α cannot activate JNK in MKK4 and MKK7 double-knockout MEFs ( Map2k4 −/− ; Map2k7 −/−”
TLR activation of the transcription factor XBP1 regulates innate immune responses in macrophages
Martinon, F., Chen, X., Lee, A.-H., & Glimcher, L. H. (2010) · Nature Immunology · doi:10.1038/ni.1857 · Cited by 996
p38MAPK: stress responses from molecular mechanisms to therapeutics
Coulthard, L. R., White, D. E., Jones, D. L., McDermott, M. F., & Burchill, S. A. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.06.005 · Cited by 691
Sriburi, R., Jackowski, S., Mori, K., & Brewer, J. W. (2004) · The Journal of Cell Biology · doi:10.1083/jcb.200406136 · Cited by 653
Solinas, G., Vilcu, C., Neels, J. G., Bandyopadhyay, G. K., Luo, J.-L., Naugler, W., Grivennikov, S., Wynshaw-Boris, A., Scadeng, M., Olefsky, J. M., et al. (2007) · Cell Metabolism · doi:10.1016/j.cmet.2007.09.011 · Cited by 513
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347
Cited by
Endoplasmic reticulum stress signalling-from basic mechanisms to clinical applications
Almanza, A., Carlesso, A., Chintha, C., Creedican, S., Doultsinos, D., Leuzzi, B., Luís, A., McCarthy, N., Montibeller, L., More, S., et al. (2019) · The FEBS Journal · doi:10.1111/febs.14608 · Cited by 1,034
Mechanisms of insulin resistance in obesity
Ye, J. (2013) · Frontiers of Medicine · doi:10.1007/s11684-013-0262-6 · Cited by 699
The mechanistic target of rapamycin: the grand conducTOR of metabolism and aging
Kennedy, B. K., & Lamming, D. W. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.05.009 · Cited by 544
Role of Leptin in Inflammation and Vice Versa
Pérez-Pérez, A., Sánchez-Jiménez, F., Vilariño-García, T., & Sánchez-Margalet, V. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21165887 · Cited by 330
Roles of XBP1s in Transcriptional Regulation of Target Genes
Park, S.-M., Kang, T.-I., & So, J.-S. (2021) · Biomedicines · doi:10.3390/biomedicines9070791 · Cited by 258
Self-citationWu, R., Zhang, Q.-H., Lu, Y.-J., Ren, K., & Yi, G.-H. (2015) · DNA and Cell Biology · doi:10.1089/dna.2014.2552 · Cited by 116
Taylor, R. C. (2016) · Brain Research · doi:10.1016/j.brainres.2016.04.017 · Cited by 83
Tsuneki, H., Tokai, E., Nakamura, Y., Takahashi, K., Fujita, M., Asaoka, T., Kon, K., Anzawa, Y., Wada, T., Takasaki, I., et al. (2015) · Diabetes · doi:10.2337/db14-0695 · Cited by 73
Bartoszewska, S., Cabaj, A., Dąbrowski, M., Collawn, J. F., & Bartoszewski, R. (2019) · The FASEB Journal · doi:10.1096/fj.201900600rr · Cited by 45
Hypothalamic orexin prevents non-alcoholic steatohepatitis and hepatocellular carcinoma in obesity
Tsuneki, H., Maeda, T., Takata, S., Sugiyama, M., Otsuka, K., Ishizuka, H., Onogi, Y., Tokai, E., Koshida, C., Kon, K., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111497 · Cited by 21
Metadata
- Authors
- Lee, J., Sun, C., Zhou, Y., Lee, J., Gokalp, D., Herrema, H., Park, S. W., Davis, R. J., & Ozcan, U.
- Venue
- Nature Medicine
- Published
- 2011-09-04
- Volume
- 17
- Issue
- 10
- Pages
- 1251-1260
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2133230812
- Cited by
- 208
- References
- 11
- FWCI
- 7.08
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
