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. 2018 Mar 15;8:4655. doi: 10.1038/s41598-018-23092-0

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Summary of the signaling pathways involved in PACAP stimulation of PRL promoter activity in αT3-1 Cells via PAC1 receptor. In αT3-1 cells, PACAP stimulate PRL promoter activity through PAC1 receptor. PACAP induction of grass carp promoter activity was mediated by AC/cAMP/PKA pathway, with a crosstalk to the CaM/CaM K-II cascade via VSCC activation and [Ca²⁺]e entry. Intracellular Ca²⁺ release followed by PLC/IP3 activation also mediates the regulation of CaM/CaM K-II on PRL gene transcription. Moreover, PI3K/Akt and p70S6K signaling was involved in the post-receptor signaling of PACAP induction of PRL gene transcription. These signaling cascades triggered by PACAP stimulation could induce PRL promoter activation via the transcription factor CREB.