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Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes.

Jonas, KC; Melrose, T; Thompson, IR; Baxter, GF; Lipscomb, VJ; Niessen, SJ; Lawson, C; McArdle, CA; Roberson, MS; McGonnell, IM; et al. Jonas, KC; Melrose, T; Thompson, IR; Baxter, GF; Lipscomb, VJ; Niessen, SJ; Lawson, C; McArdle, CA; Roberson, MS; McGonnell, IM; Wheeler-Jones, CP; Fowkes, RC (2017) Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes. Cell Tissue Res, 369 (3). pp. 567-578. ISSN 1432-0878 https://doi.org/10.1007/s00441-017-2624-x
SGUL Authors: Jonas, Kim Carol

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Abstract

The natriuretic peptides, Atrial-, B-type and C-type natriuretric peptides (ANP, BNP, CNP), are regulators of many endocrine tissues and exert their effects predominantly through the activation of their specific guanylyl cyclase receptors (GC-A and GC-B) to generate cGMP. Whereas cGMP-independent signalling has been reported in response to natriuretic peptides, this is mediated via either the clearance receptor (Npr-C) or a renal-specific NPR-Bi isoform, which both lack intrinsic guanylyl cyclase activity. Here, we report evidence of GC-B-dependent cGMP-independent signalling in pituitary GH3 cells. Stimulation of GH3 cells with CNP resulted in a rapid and sustained enhancement of ERK1/2 phosphorylation (P-ERK1/2), an effect that was not mimicked by dibutryl-cGMP. Furthermore, CNP-stimulated P-ERK1/2 occurred at concentrations below that required for cGMP accumulation. The effect of CNP on P-ERK1/2 was sensitive to pharmacological blockade of MEK (U0126) and Src kinases (PP2). Silencing of the GC-B1 and GC-B2 splice variants of the GC-B receptor by using targeted short interfering RNAs completely blocked the CNP effects on P-ERK1/2. CNP failed to alter GH3 cell proliferation or cell cycle distribution but caused a concentration-dependent increase in the activity of the human glycoprotein α-subunit promoter (αGSU) in a MEK-dependent manner. Finally, CNP also activated the p38 and JNK MAPK pathways in GH3 cells. These findings reveal an additional mechanism of GC-B signalling and suggest additional biological roles for CNP in its target tissues.

Item Type: Article
Additional Information: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
Keywords: ERK1/2, Guanylyl cyclase, Natriuretic, Pituitary, cGMP, Neurology & Neurosurgery, 1116 Medical Physiology
SGUL Research Institute / Research Centre: Academic Structure > Institute of Medical & Biomedical Education (IMBE)
Academic Structure > Institute of Medical & Biomedical Education (IMBE) > Centre for Biomedical Education (INMEBE)
Journal or Publication Title: Cell Tissue Res
ISSN: 1432-0878
Language: eng
Dates:
DateEvent
September 2017Published
27 April 2017Published Online
2 February 2017Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
BBD0015601Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
BB/L002795/1Biotechnology and Biological Sciences Research Councilhttp://dx.doi.org/10.13039/501100000268
WT093257MAWellcome Trusthttp://dx.doi.org/10.13039/100004440
PubMed ID: 28451751
Go to PubMed abstract
URI: https://openaccess.sgul.ac.uk/id/eprint/108820
Publisher's version: https://doi.org/10.1007/s00441-017-2624-x

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