TY - JOUR
T1 - PTP1B regulates leptin signal transduction in vivo
AU - Zabolotny, Janice M.
AU - Bence-Hanulec, Kendra K.
AU - Stricker-Krongrad, Alain
AU - Haj, Fawaz
AU - Wang, Yongping
AU - Minokoshi, Yasuhiko
AU - Kim, Young Bum
AU - Elmquist, Joel K.
AU - Tartaglia, Louis A.
AU - Kahn, Barbara B.
AU - Neel, Benjamin G.
N1 - Funding Information:
We thank Odile Peroni, Brian Choi, and Charlotte Lee for help with experiments, Nick Tonks (Cold Spring Harbor Laboratory) for PTP1B retroviruses, Martin Myers and Dwayne Barber for antibodies, Christian Bjorbaek for leptin receptor constructs, Jeff Flier and Brad Lowell for helpful discussions, and Lew Cantley for comments on the manuscript. This work was supported by National Institutes of Health grants R01 CA49512 and P01 DK50654 to B.G.N., P30 DK57521 and R01 DK43051 to B.B.K, R01 DK53301 and R01 MH61583 to J.K.E, P01 DK56116 to B.B.K. and J.K.E., and grants from the American Diabetes Association to B.B.K. and B.G.N. J.M.Z. was supported by Individual NRSA DK09903 and K.K.B.-H. by Institutional NRSA CA81156 and Individual NRSA DK60287 from the NIH.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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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U2 - 10.1016/S1534-5807(02)00148-X
DO - 10.1016/S1534-5807(02)00148-X
M3 - Article
C2 - 11970898
AN - SCOPUS:18344379861
SN - 1534-5807
VL - 2
SP - 489
EP - 495
JO - Developmental Cell
JF - Developmental Cell
IS - 4
ER -