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 | ||||||||||||
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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 and Allied Health Education (IMBE) Academic Structure > Institute of Medical, Biomedical and Allied Health Education (IMBE) > Centre for Biomedical Education (INMEBE) |
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Journal or Publication Title: | Cell Tissue Res | ||||||||||||
ISSN: | 1432-0878 | ||||||||||||
Language: | eng | ||||||||||||
Publisher License: | Creative Commons: Attribution 4.0 | ||||||||||||
Projects: |
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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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