Roles of Pyk2 in signal transduction after gonadotropin‐releasing hormone receptor stimulation.

Autor: Okitsu‐Sakurayama, Shiho, Higa‐Nakamine, Sayomi, Torihara, Hidetsugu, Higashiyama, Shigeki, Yamamoto, Hideyuki
Předmět:
Zdroj: Journal of Cellular Physiology; Apr2021, Vol. 236 Issue 4, p3033-3043, 11p
Abstrakt: The receptor for gonadotropin‐releasing hormone (GnRH) is highly expressed in hypothalamic neurons. It has been reported that GnRH treatment of cultured GnRH neurons (GT1‐7 cells) activated proline‐rich tyrosine kinase 2 (Pyk2), and Pyk2 was involved in the activation of extracellular signal‐regulated protein kinase 1 (ERK1) and ERK2 (ERK1/2). In the present study, we first examined the possibility that GnRH treatment might activate epidermal growth factor receptor (EGFR). We found that activation of EGFR after GnRH treatment for 5 min was much less than after EGF or heparin‐binding EGF treatment. Next, we examined whether or not Pyk2 bound to growth factor receptor‐binding protein 2 (Grb2). We overexpressed FLAG‐fused Pyk2 in GT1‐7 cells, and immunoprecipitated Pyk2 using an anti‐FLAG antibody. The binding of Pyk2 to Grb2 was detected only after GnRH treatment. In contrast, a site‐directed mutant of Pyk2 wherein tyrosine 881 was mutated to phenylalanine did not bind to Grb2. Studies with small interfering RNA and inhibitors indicated that the activation of Grb2/Ras/Raf/MEK was a major pathway to ERK1/2 activation after the short‐term treatment of GT1‐7 cells with GnRH. [ABSTRACT FROM AUTHOR]
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