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Publication : PTP1B regulates leptin signal transduction in vivo.

First Author  Zabolotny JM Year  2002
Journal  Dev Cell Volume  2
Issue  4 Pages  489-95
PubMed ID  11970898 Mgi Jnum  J:75970
Mgi Id  MGI:2178165 Doi  10.1016/s1534-5807(02)00148-x
Citation  Zabolotny JM, et al. (2002) PTP1B Regulates Leptin Signal Transduction In Vivo. Dev Cell 2(4):489-95
abstractText  Mice lacking the protein-tyrosine phosphatase PTP1B are hypersensitive to insulin and resistant to obesity. However, the molecular basis for resistance to obesity has been unclear. Here we show that PTP1B regulates leptin signaling. In transfection studies, PTP1B dephosphorylates the leptin receptor-associated kinase, Jak2. PTP1B is expressed in hypothalamic regions harboring leptin-responsive neurons. Compared to wild-type littermates, PTP1B(-/-) mice have decreased leptin/body fat ratios, leptin hypersensitivity, and enhanced leptin-induced hypothalamic Stat3 tyrosyl phosphorylation. Gold thioglucose treatment, which ablates leptin-responsive hypothalamic neurons, partially overcomes resistance to obesity in PTP1B(-/-) mice. Our data indicate that PTP1B regulates leptin signaling in vivo, likely by targeting Jak2. PTP1B may be a novel target to treat leptin resistance in obesity.
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