Activation of Pyk2 by CaM kinase II in cultured hypothalamic neurons and gonadotroph cells

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.

Source: Journal of Cellular Physiology - November 11, 2018 Category: Cytology Authors: Shiho Okitsu ‐Sakurayama, Sayomi Higa‐Nakamine, Hidetsugu Torihara, Hana Takahashi, Shigeki Higashiyama, Hideyuki Yamamoto Tags: ORIGINAL RESEARCH ARTICLE Source Type: research