C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.

Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Catherine Denis, Kathleen Deiteren, Anneleen Mortier, Amel Tounsi, Erik Fransen, Paul Proost, Jean-Christophe Renauld, Anne-Marie Lambeir
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/57342576b21a48938c1554d41bc9bc3c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:57342576b21a48938c1554d41bc9bc3c
record_format	dspace
spelling	oai:doaj.org-article:57342576b21a48938c1554d41bc9bc3c2021-11-18T07:24:11ZC-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.1932-620310.1371/journal.pone.0034199https://doaj.org/article/57342576b21a48938c1554d41bc9bc3c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22479563/?tool=EBIhttps://doaj.org/toc/1932-6203Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system.Catherine DenisKathleen DeiterenAnneleen MortierAmel TounsiErik FransenPaul ProostJean-Christophe RenauldAnne-Marie LambeirPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 3, p e34199 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine Denis Kathleen Deiteren Anneleen Mortier Amel Tounsi Erik Fransen Paul Proost Jean-Christophe Renauld Anne-Marie Lambeir C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
description	Carboxypeptidase M (CPM) targets the basic amino acids arginine and lysine present at the C-terminus of peptides or proteins. CPM is thought to be involved in inflammatory processes. This is corroborated by CPM-mediated trimming and modulation of inflammatory factors, and expression of the protease in inflammatory environments. Since the function of CPM in and beyond inflammation remains mainly undefined, the identification of natural substrates can aid in discovering the (patho)physiological role of CPM. CCL1/I-309, with its three C-terminal basic amino acids, forms a potential natural substrate for CPM. CCL1 plays a role not only in inflammation but also in apoptosis, angiogenesis and tumor biology. Enzymatic processing differently impacts the biological activity of chemokines thereby contributing to the complex regulation of the chemokine system. The aim of the present study was to investigate whether (i) CCL1/I-309 is prone to trimming by CPM, and (ii) the biological activity of CCL1 is altered after C-terminal proteolytic processing. CCL1 was identified as a novel substrate for CPM in vitro using mass spectrometry. C-terminal clipping of CCL1 augmented intracellular calcium release mediated by CCR8 but reduced the binding of CCL1 to CCR8. In line with the higher intracellular calcium release, a pronounced increase of the anti-apoptotic activity of CCL1 was observed in the BW5147 cellular model. CCR8 signaling, CCR8 binding and anti-apoptotic activity were unaffected when CPM was exposed to the carboxypeptidase inhibitor DL-2-mercaptomethyl-3-guanidino-ethylthiopropanoic acid. The results of this study suggest that CPM is a likely candidate for the regulation of biological processes relying on the CCL1-CCR8 system.
format	article
author	Catherine Denis Kathleen Deiteren Anneleen Mortier Amel Tounsi Erik Fransen Paul Proost Jean-Christophe Renauld Anne-Marie Lambeir
author_facet	Catherine Denis Kathleen Deiteren Anneleen Mortier Amel Tounsi Erik Fransen Paul Proost Jean-Christophe Renauld Anne-Marie Lambeir
author_sort	Catherine Denis
title	C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
title_short	C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
title_full	C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
title_fullStr	C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
title_full_unstemmed	C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.
title_sort	c-terminal clipping of chemokine ccl1/i-309 enhances ccr8-mediated intracellular calcium release and anti-apoptotic activity.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/57342576b21a48938c1554d41bc9bc3c
work_keys_str_mv	AT catherinedenis cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT kathleendeiteren cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT anneleenmortier cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT ameltounsi cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT erikfransen cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT paulproost cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT jeanchristopherenauld cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity AT annemarielambeir cterminalclippingofchemokineccl1i309enhancesccr8mediatedintracellularcalciumreleaseandantiapoptoticactivity
_version_	1718423475508477952

C-terminal clipping of chemokine CCL1/I-309 enhances CCR8-mediated intracellular calcium release and anti-apoptotic activity.

Ejemplares similares