PTP1B regulates leptin signal transduction in vivo

Janice M. Zabolotny; Kendra K. Bence-Hanulec; Alain Stricker-Krongrad; Fawaz Haj; Yongping Wang; Yasuhiko Minokoshi; Young Bum Kim; Joel K. Elmquist; Louis A. Tartaglia; Barbara B. Kahn; Benjamin G. Neel

doi:10.1016/S1534-5807(02)00148-X

PTP1B regulates leptin signal transduction in vivo

Janice M. Zabolotny, Kendra K. Bence-Hanulec, Alain Stricker-Krongrad, Fawaz Haj, Yongping Wang, Yasuhiko Minokoshi, Young Bum Kim, Joel K. Elmquist, Louis A. Tartaglia, Barbara B. Kahn, Benjamin G. Neel

Research output: Contribution to journal › Article

618 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	489-495
Number of pages	7
Journal	Developmental Cell
Volume	2
Issue number	4
DOIs	https://doi.org/10.1016/S1534-5807(02)00148-X
State	Published - 2002
Externally published	Yes

Fingerprint

ASJC Scopus subject areas

Developmental Biology

Cite this

Zabolotny, J. M., Bence-Hanulec, K. K., Stricker-Krongrad, A., Haj, F., Wang, Y., Minokoshi, Y., Kim, Y. B., Elmquist, J. K., Tartaglia, L. A., Kahn, B. B., & Neel, B. G. (2002). PTP1B regulates leptin signal transduction in vivo. Developmental Cell, 2(4), 489-495. https://doi.org/10.1016/S1534-5807(02)00148-X

PTP1B regulates leptin signal transduction in vivo. / Zabolotny, Janice M.; Bence-Hanulec, Kendra K.; Stricker-Krongrad, Alain; Haj, Fawaz; Wang, Yongping; Minokoshi, Yasuhiko; Kim, Young Bum; Elmquist, Joel K.; Tartaglia, Louis A.; Kahn, Barbara B.; Neel, Benjamin G.

In: Developmental Cell, Vol. 2, No. 4, 2002, p. 489-495.

Research output: Contribution to journal › Article

@article{00e0b345262c44c79eec50d1cbed82c2,

title = "PTP1B regulates leptin signal transduction in vivo",

abstract = "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.",

author = "Zabolotny, {Janice M.} and Bence-Hanulec, {Kendra K.} and Alain Stricker-Krongrad and Fawaz Haj and Yongping Wang and Yasuhiko Minokoshi and Kim, {Young Bum} and Elmquist, {Joel K.} and Tartaglia, {Louis A.} and Kahn, {Barbara B.} and Neel, {Benjamin G.}",

year = "2002",

doi = "10.1016/S1534-5807(02)00148-X",

language = "English (US)",

volume = "2",

pages = "489--495",

journal = "Developmental Cell",

issn = "1534-5807",

publisher = "Cell Press",

number = "4",

}

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=18344379861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18344379861&partnerID=8YFLogxK

U2 - 10.1016/S1534-5807(02)00148-X

DO - 10.1016/S1534-5807(02)00148-X

M3 - Article

C2 - 11970898

AN - SCOPUS:18344379861

VL - 2

SP - 489

EP - 495

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 4

ER -

Access to Document

10.1016/S1534-5807(02)00148-X