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Analysis of Tyr to Phe and the fa/fa leptin receptor mutations in the PC12 cell line

Sven Eyckerman UGent, Wim Waelput, Annick Verhee UGent, Daniël Broekaert, Joël Vandekerckhove and Jan Tavernier UGent (1999) EUROPEAN CYTOKINE NETWORK. 10(4). p.549-556
abstract
Weight regulation through body-fat content and energy homeostasis, is regulated mainly through the actions of leptin, Herein, we analyse the effect of mutations in the mouse leptin receptor using the PC12 pheochromocytoma cell line as a model system. Both the induction of pancreatitis associated protein 1 and metallothionein-II, two leptin regulated genes in PC12, was evaluated. Tyr to Phe mutations in the cytoplasmic tail of the mouse leptin receptor confirmed the critical role of Tyr1138 (a YxxQ motif) and STAT-3 activation for induction of leptin-induced genes in PC12, In addition, the Tyr985Phe mutation showed enhanced responsiveness to leptin, which was even more pronounced in combination with Tyr1077Phe. The short isoform of the leptin receptor showed complete loss of stimulation of both genes. In contrast, a leptin receptor devoid of all Tyr residues in its cytoplasmic tail was still capable of a limited induction of the PAP 1 gene. A mutant mouse leptin receptor containing the fa/fa mutation showed constitutive signalling and impaired responsiveness to leptin, Treatment with the adenylate cyclase activator forskolin alone, in the absence of leptin was sufficient to obtain full induction of both genes.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
subject
keyword
signal transduction, leptin, leptin receptor, IN-SITU HYBRIDIZATION, OB-R, EXTRACELLULAR DOMAIN, FATTY MUTATION, DIABETIC MICE, MESSENGER-RNA, DB/DB MICE, RAT FATTY, EXPRESSION, GENE
journal title
EUROPEAN CYTOKINE NETWORK
Eur. Cytokine Netw.
volume
10
issue
4
pages
549 - 556
Web of Science type
Article
Web of Science id
000084043200011
ISSN
1148-5493
language
English
UGent publication?
yes
classification
A1
id
175550
handle
http://hdl.handle.net/1854/LU-175550
alternative location
http://www.jle.com/en/revues/bio_rech/ecn/e-docs/00/01/5F/DD/article.phtml
date created
2004-01-14 13:40:00
date last changed
2016-12-19 15:38:07
@article{175550,
  abstract     = {Weight regulation through body-fat content and energy homeostasis, is regulated mainly through the actions of leptin, Herein, we analyse the effect of mutations in the mouse leptin receptor using the PC12 pheochromocytoma cell line as a model system. Both the induction of pancreatitis associated protein 1 and metallothionein-II, two leptin regulated genes in PC12, was evaluated. Tyr to Phe mutations in the cytoplasmic tail of the mouse leptin receptor confirmed the critical role of Tyr1138 (a YxxQ motif) and STAT-3 activation for induction of leptin-induced genes in PC12, In addition, the Tyr985Phe mutation showed enhanced responsiveness to leptin, which was even more pronounced in combination with Tyr1077Phe. The short isoform of the leptin receptor showed complete loss of stimulation of both genes. In contrast, a leptin receptor devoid of all Tyr residues in its cytoplasmic tail was still capable of a limited induction of the PAP 1 gene. A mutant mouse leptin receptor containing the fa/fa mutation showed constitutive signalling and impaired responsiveness to leptin, Treatment with the adenylate cyclase activator forskolin alone, in the absence of leptin was sufficient to obtain full induction of both genes.},
  author       = {Eyckerman, Sven and Waelput, Wim and Verhee, Annick and Broekaert, Dani{\"e}l and Vandekerckhove, Jo{\"e}l and Tavernier, Jan},
  issn         = {1148-5493},
  journal      = {EUROPEAN CYTOKINE NETWORK},
  keyword      = {signal transduction,leptin,leptin receptor,IN-SITU HYBRIDIZATION,OB-R,EXTRACELLULAR DOMAIN,FATTY MUTATION,DIABETIC MICE,MESSENGER-RNA,DB/DB MICE,RAT FATTY,EXPRESSION,GENE},
  language     = {eng},
  number       = {4},
  pages        = {549--556},
  title        = {Analysis of Tyr to Phe and the fa/fa leptin receptor mutations in the PC12 cell line},
  url          = {http://www.jle.com/en/revues/bio\_rech/ecn/e-docs/00/01/5F/DD/article.phtml},
  volume       = {10},
  year         = {1999},
}

Chicago
Eyckerman, Sven, Wim Waelput, Annick Verhee, Daniël Broekaert, Joël Vandekerckhove, and Jan Tavernier. 1999. “Analysis of Tyr to Phe and the Fa/fa Leptin Receptor Mutations in the PC12 Cell Line.” European Cytokine Network 10 (4): 549–556.
APA
Eyckerman, S., Waelput, W., Verhee, A., Broekaert, D., Vandekerckhove, J., & Tavernier, J. (1999). Analysis of Tyr to Phe and the fa/fa leptin receptor mutations in the PC12 cell line. EUROPEAN CYTOKINE NETWORK, 10(4), 549–556.
Vancouver
1.
Eyckerman S, Waelput W, Verhee A, Broekaert D, Vandekerckhove J, Tavernier J. Analysis of Tyr to Phe and the fa/fa leptin receptor mutations in the PC12 cell line. EUROPEAN CYTOKINE NETWORK. 1999;10(4):549–56.
MLA
Eyckerman, Sven, Wim Waelput, Annick Verhee, et al. “Analysis of Tyr to Phe and the Fa/fa Leptin Receptor Mutations in the PC12 Cell Line.” EUROPEAN CYTOKINE NETWORK 10.4 (1999): 549–556. Print.