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Cited by 208

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 access
Lee, Jaemin, Sun, Cheng, Zhou, Yingjiang, Lee, Justin, Gokalp, Deniz, Herrema, Hilde, Park, Sang Won, Davis, Roger J, Ozcan, Umut·2011·Nature Medicine
DOI 10.1038/nm.2449
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Abstract

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.

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Crossref · 10.1038/nm.2449

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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
Publisher
Springer Science and Business Media LLC
Published
2011-09-04
Volume
17
Issue
10
Pages
1251-1260
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm.2449
OpenAlex
W2133230812
Cited by
208
References
11
FWCI
7.08
Type
journal article
Language
en
Open access
green

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