Neurokinin B Induces c-fos Transcription via Protein Kinase C and Activation of Serum Response Factor and Elk-1 in Immortalized GnRH Neurons
| Autor: | Christine A. Glidewell-Kenney, Adaku M. Uzo-Okereke, Djurdjica Coss, Navarre Gutierrez-Reed, Crystal Trang, Pamela L. Mellon, Paul P. Shao |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Serum Response Factor
medicine.medical_specialty Transcription Genetic Neurokinin B Gonadotropin-releasing hormone Biology Gonadotropin-Releasing Hormone Mice chemistry.chemical_compound Endocrinology Internal medicine Serum response factor medicine Animals Protein Kinase C Protein kinase C Cell Line Transformed ets-Domain Protein Elk-1 Neurons GnRH Neuron Neuroendocrinology Serum Response Element Rats Up-Regulation chemistry STAT protein Signal transduction Proto-Oncogene Proteins c-fos Signal Transduction |
| Zdroj: | Endocrinology. 155:3909-3919 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2014-1263 |
| Popis: | Mutations in neurokinin B (NKB) and its receptor, NK3R, were identified in human patients with hypogonadotropic hypogonadism, a disorder characterized by lack of puberty and infertility. Further studies have suggested that NKB acts at the level of the hypothalamus to control GnRH neuron activity, either directly or indirectly. We recently reported that treatment with senktide, a NK3R agonist, induced GnRH secretion and expression of c-fos mRNA in GT1-7 cells. Here, we map the responsive region in the murine c-fos promoter to between −400 and −200 bp, identify the signal transducer and activator of transcription (STAT) (−345) and serum response element (−310) sites as required for induction, a modulatory role for the Ets site (−318), and show that induction is protein kinase C dependent. Using gel shift and Gal4 assays, we further show that phosphorylation of Elk-1 leads to binding to DNA in complex with serum response factor at serum response element and Ets sites within the c-fos promoter. Thus, we determine molecular mechanisms involved in NKB regulation of c-fos induction, which may play a role in modulation of GnRH neuron activation. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|