Activation of Pyk2 by CaM kinase II in cultured hypothalamic neurons and gonadotroph cells
| Autor: | Hideyuki Yamamoto, Shigeki Higashiyama, Sayomi Higa-Nakamine, Hana Takahashi, Shiho Okitsu-Sakurayama, Hidetsugu Torihara |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
MAPK/ERK pathway endocrine system Physiology MAP Kinase Signaling System Clinical Biochemistry Hypothalamus Gonadotropin-releasing hormone Gonadotrophs Cell Line Gonadotropin-Releasing Hormone 03 medical and health sciences Mice 0302 clinical medicine Ca2+/calmodulin-dependent protein kinase Animals Protein kinase A Receptor Extracellular Signal-Regulated MAP Kinases G protein-coupled receptor Neurons Chemistry Kinase Cell Biology Cell biology Enzyme Activation 030104 developmental biology Focal Adhesion Kinase 2 Tyrosine kinase 2 030220 oncology & carcinogenesis Calcium-Calmodulin-Dependent Protein Kinase Type 2 hormones hormone substitutes and hormone antagonists Receptors LHRH Signal Transduction |
| Zdroj: | Journal of cellular physiology. 234(5) |
| ISSN: | 1097-4652 |
| Popis: | Gonadotropin-releasing hormone (GnRH) is secreted from hypothalamic GnRH neurons and stimulates a GnRH receptor in gonadotroph cells and GnRH neurons. The GnRH receptor belongs to the G-protein-coupled receptors, and stimulation of the GnRH receptor activates extracellular signal-regulated protein kinase (ERK). We reported previously that the δ2 isoform of Ca2+ /calmodulin-dependent protein kinase II (CaM kinase IIδ2) was involved in GnRH-induced ERK activation in cultured GnRH neurons (GT1-7 cells). Recently, we found that GnRH treatment of GT1-7 cells activated proline-rich tyrosine kinase 2 (Pyk2), and Pyk2 was involved in ERK activation. In the current study, we examined the possibility that CaM kinase IIδ2 might activate Pyk2. Knockdown of CaM kinase IIδ2 and KN93, an inhibitor of CaM kinases, inhibited the GnRH-induced activation of Pyk2. In the case of cultured gonadotroph cells (αT3-1 cells), knockdown of CaM kinase IIβ'e inhibited GnRH-induced Pyk2 activation. In addition, our inhibitor studies indicated that Pyk2 and CaM kinase II were involved in the GnRH-induced shedding of proHB-EGF in GT1-7 cells. These results suggested that CaM kinase II activated the ERK pathway through Pyk2 activation and HB-EGF production in response to GnRH. |
| Databáze: | OpenAIRE |
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