Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling

Ceren Ozek, Scott E. Kanoski, Zhong-Yin Zhang, Harvey J. Grill, Kendra K. Bence

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1-/- mice exhibit enhanced TrkB phosphorylation, and Ptpn1-/- mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

Original languageEnglish
Pages (from-to)31682-31692
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number46
DOIs
StatePublished - Nov 14 2014

Fingerprint

Non-Receptor Type 1 Protein Tyrosine Phosphatase
trkB Receptor
Tropomyosin
Brain-Derived Neurotrophic Factor
Phosphotransferases
Brain
Phosphorylation
tropomyosin kinase
Nutrition
Leptin
Neuroblastoma
Obesity
Chemical activation
Diet

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling. / Ozek, Ceren; Kanoski, Scott E.; Zhang, Zhong-Yin; Grill, Harvey J.; Bence, Kendra K.

In: Journal of Biological Chemistry, Vol. 289, No. 46, 14.11.2014, p. 31682-31692.

Research output: Contribution to journalArticle

@article{4fd193d213614716a1e75928d8a3f28f,
title = "Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling",
abstract = "Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1-/- mice exhibit enhanced TrkB phosphorylation, and Ptpn1-/- mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.",
author = "Ceren Ozek and Kanoski, {Scott E.} and Zhong-Yin Zhang and Grill, {Harvey J.} and Bence, {Kendra K.}",
year = "2014",
month = "11",
day = "14",
doi = "10.1074/jbc.M114.603621",
language = "English",
volume = "289",
pages = "31682--31692",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "46",

}

TY - JOUR

T1 - Protein-tyrosine phosphatase 1B (PTP1B) is a novel regulator of central brain-derived neurotrophic factor and tropomyosin receptor kinase B (TrkB) signaling

AU - Ozek, Ceren

AU - Kanoski, Scott E.

AU - Zhang, Zhong-Yin

AU - Grill, Harvey J.

AU - Bence, Kendra K.

PY - 2014/11/14

Y1 - 2014/11/14

N2 - Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1-/- mice exhibit enhanced TrkB phosphorylation, and Ptpn1-/- mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

AB - Neuronal protein-tyrosine phosphatase 1B (PTP1B) deficiency in mice results in enhanced leptin signaling and protection from diet-induced obesity; however, whether additional signaling pathways in the brain contribute to the metabolic effects of PTP1B deficiency remains unclear. Here, we show that the tropomyosin receptor kinase B (TrkB) receptor is a direct PTP1B substrate and implicate PTP1B in the regulation of the central brain-derived neurotrophic factor (BDNF) signaling. PTP1B interacts with activated TrkB receptor in mouse brain and human SH-SY5Y neuroblastoma cells. PTP1B overexpression reduces TrkB phosphorylation and activation of downstream signaling pathways, whereas PTP1B inhibition augments TrkB signaling. Notably, brains of Ptpn1-/- mice exhibit enhanced TrkB phosphorylation, and Ptpn1-/- mice are hypersensitive to central BDNF-induced increase in core temperature. Taken together, our findings demonstrate that PTP1B is a novel physiological regulator of TrkB and that enhanced BDNF/TrkB signaling may contribute to the beneficial metabolic effects of PTP1B deficiency.

UR - http://www.scopus.com/inward/record.url?scp=84911030977&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84911030977&partnerID=8YFLogxK

U2 - 10.1074/jbc.M114.603621

DO - 10.1074/jbc.M114.603621

M3 - Article

C2 - 25288805

AN - SCOPUS:84911030977

VL - 289

SP - 31682

EP - 31692

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 46

ER -