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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 (UGent) , Annick Verhee (UGent) , Daniël Broekaert (UGent) , Joël Vandekerckhove (UGent) and Jan Tavernier (UGent)
(1999) EUROPEAN CYTOKINE NETWORK. 10(4). p.549-556
Author
Organization
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.
Keywords
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

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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.
@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},
}

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