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dc.contributor.authorRobertson, Scott
dc.contributor.authorIshida-Takahashi, Ryoko
dc.contributor.authorTawara, Isao
dc.contributor.authorHu, Jiang
dc.contributor.authorPatterson, Christa M.
dc.contributor.authorJones, Justin C.
dc.contributor.authorKulkarni, Rohit Narayan
dc.contributor.authorMyers, Martin G.
dc.date.accessioned2011-12-29T05:42:54Z
dc.date.issued2010
dc.identifier.citationRobertson, Scott, Ryoko Ishida-Takahashi, Isao Tawara, Jiang Hu, Christa M. Patterson, Justin C. Jones, Rohit N. Kulkarni, and Martin G. Myers. 2010. Insufficiency of Janus kinase 2-autonomous leptin receptor signals for most physiologic leptin actions. Diabetes 59(4): 782-790.en_US
dc.identifier.issn0012-1797en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:5978699
dc.description.abstractOBJECTIVE: Leptin acts via its receptor (LepRb) to signal the status of body energy stores. Leptin binding to LepRb initiates signaling by activating the associated Janus kinase 2 (Jak2) tyrosine kinase, which promotes the phosphorylation of tyrosine residues on the intracellular tail of LepRb. Two previously examined LepRb phosphorylation sites mediate several, but not all, aspects of leptin action, leading us to hypothesize that Jak2 signaling might contribute to leptin action independently of LepRb phosphorylation sites. We therefore determined the potential role in leptin action for signals that are activated by Jak2 independently of LepRb phosphorylation (Jak2-autonomous signals). RESEARCH DESIGN AND METHODS: We inserted sequences encoding a truncated LepRb mutant (LepRb\(^{\Delta65c}\), which activates Jak2 normally, but is devoid of other LepRb intracellular sequences) into the mouse Lepr locus. We examined the leptin-regulated physiology of the resulting \(\Delta/\Delta\) mice relative to LepRb-deficient \(db/db\) animals. RESULTS: The \(\Delta/\Delta\) animals were similar to \(db/db\) animals in terms of energy homeostasis, neuroendocrine and immune function, and regulation of the hypothalamic arcuate nucleus, but demonstrated modest improvements in glucose homeostasis. CONCLUSIONS: The ability of Jak2-autonomous LepRb signals to modulate glucose homeostasis in \(\Delta/\Delta\) animals suggests a role for these signals in leptin action. Because Jak2-autonomous LepRb signals fail to mediate most leptin action, however, signals from other LepRb intracellular sequences predominate.en_US
dc.language.isoen_USen_US
dc.publisherAmerican Diabetes Associationen_US
dc.relation.isversionofdoi://10.2337/db09-1556en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC2844825/pdf/en_US
dash.licenseLAA
dc.titleInsufficiency of Janus Kinase 2-Autonomous Leptin Receptor Signals for Most Physiologic Leptin Actionsen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalDiabetesen_US
dash.depositing.authorKulkarni, Rohit Narayan
dc.date.available2011-12-29T05:42:54Z
dash.affiliation.otherHMS^Medicine-Brigham and Women's Hospitalen_US
dc.identifier.doi10.2337/db09-1556*
dash.contributor.affiliatedKulkarni, Rohit


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