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

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 si...

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Autores principales: Jonas, Kim C., Melrose, Timothy, Thompson, Iain R., Baxter, Gary F., Lipscomb, Victoria J., Niessen, Stijn J., Lawson, Charlotte, McArdle, Craig A., Roberson, Mark S., McGonnell, Imelda M., Wheeler-Jones, Caroline P., Fowkes, Robert C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579180/
https://www.ncbi.nlm.nih.gov/pubmed/28451751
http://dx.doi.org/10.1007/s00441-017-2624-x
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author Jonas, Kim C.
Melrose, Timothy
Thompson, Iain R.
Baxter, Gary F.
Lipscomb, Victoria J.
Niessen, Stijn J.
Lawson, Charlotte
McArdle, Craig A.
Roberson, Mark S.
McGonnell, Imelda M.
Wheeler-Jones, Caroline P.
Fowkes, Robert C.
author_facet Jonas, Kim C.
Melrose, Timothy
Thompson, Iain R.
Baxter, Gary F.
Lipscomb, Victoria J.
Niessen, Stijn J.
Lawson, Charlotte
McArdle, Craig A.
Roberson, Mark S.
McGonnell, Imelda M.
Wheeler-Jones, Caroline P.
Fowkes, Robert C.
author_sort Jonas, Kim C.
collection PubMed
description 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00441-017-2624-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-55791802017-09-18 Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes Jonas, Kim C. Melrose, Timothy Thompson, Iain R. Baxter, Gary F. Lipscomb, Victoria J. Niessen, Stijn J. Lawson, Charlotte McArdle, Craig A. Roberson, Mark S. McGonnell, Imelda M. Wheeler-Jones, Caroline P. Fowkes, Robert C. Cell Tissue Res Regular Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00441-017-2624-x) contains supplementary material, which is available to authorized users. Springer Berlin Heidelberg 2017-04-27 2017 /pmc/articles/PMC5579180/ /pubmed/28451751 http://dx.doi.org/10.1007/s00441-017-2624-x Text en © The Author(s) 2017 Open Access 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.
spellingShingle Regular Article
Jonas, Kim C.
Melrose, Timothy
Thompson, Iain R.
Baxter, Gary F.
Lipscomb, Victoria J.
Niessen, Stijn J.
Lawson, Charlotte
McArdle, Craig A.
Roberson, Mark S.
McGonnell, Imelda M.
Wheeler-Jones, Caroline P.
Fowkes, Robert C.
Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title_full Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title_fullStr Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title_full_unstemmed Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title_short Natriuretic peptide activation of extracellular regulated kinase 1/2 (ERK1/2) pathway by particulate guanylyl cyclases in GH3 somatolactotropes
title_sort natriuretic peptide activation of extracellular regulated kinase 1/2 (erk1/2) pathway by particulate guanylyl cyclases in gh3 somatolactotropes
topic Regular Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5579180/
https://www.ncbi.nlm.nih.gov/pubmed/28451751
http://dx.doi.org/10.1007/s00441-017-2624-x
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