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Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells

A disintegrin and metalloproteases (ADAMs) have been implicated in many processes controlling organismic development and integrity. Important substrates of ADAM proteases include growth factors, cytokines and their receptors and adhesion proteins. The inducible but irreversible cleavage of their sub...

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Autores principales: Ebsen, Henriette, Schröder, Alexandra, Kabelitz, Dieter, Janssen, Ottmar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793918/
https://www.ncbi.nlm.nih.gov/pubmed/24130797
http://dx.doi.org/10.1371/journal.pone.0076853
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author Ebsen, Henriette
Schröder, Alexandra
Kabelitz, Dieter
Janssen, Ottmar
author_facet Ebsen, Henriette
Schröder, Alexandra
Kabelitz, Dieter
Janssen, Ottmar
author_sort Ebsen, Henriette
collection PubMed
description A disintegrin and metalloproteases (ADAMs) have been implicated in many processes controlling organismic development and integrity. Important substrates of ADAM proteases include growth factors, cytokines and their receptors and adhesion proteins. The inducible but irreversible cleavage of their substrates alters cell-cell communication and signaling. The crucial role of ADAM proteases (e.g. ADAM10 and 17) for mammalian development became evident from respective knockout mice, that displayed pre- or perinatal lethality with severe defects in many organs and tissues. Although many substrates for these two ADAM proteases were identified over the last decade, the regulation of their surface appearance, their enzymatic activity and their substrate specificity are still not well understood. We therefore analyzed the constitutive and inducible surface expression of ADAM10 and ADAM17 on a variety of human T cell and tumor cell lines. We demonstrate that ADAM10 is constitutively present at comparably high levels on the majority of the tested cell types. Stimulation with phorbol ester and calcium ionophore does not significantly alter the amount of surface ADAM10, except for a slight down-regulation from T cell blasts. Using FasL shedding as a readout for ADAM10 activity, we show that PKC activation and calcium mobilization are both prerequisite for activation of ADAM10 resulting in a production of soluble FasL. In contrast to ADAM10, the close relative ADAM17 is detected at only low levels on unstimulated cells. ADAM17 surface expression on T cell blasts is rapidly induced by stimulation. Since this inducible mobilization of ADAM17 is sensitive to inhibitors of actin filament formation, we propose that ADAM17 but not ADAM10 is prestored in a subcellular compartment that is transported to the cell surface in an activation- and actin-dependent manner.
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spelling pubmed-37939182013-10-15 Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells Ebsen, Henriette Schröder, Alexandra Kabelitz, Dieter Janssen, Ottmar PLoS One Research Article A disintegrin and metalloproteases (ADAMs) have been implicated in many processes controlling organismic development and integrity. Important substrates of ADAM proteases include growth factors, cytokines and their receptors and adhesion proteins. The inducible but irreversible cleavage of their substrates alters cell-cell communication and signaling. The crucial role of ADAM proteases (e.g. ADAM10 and 17) for mammalian development became evident from respective knockout mice, that displayed pre- or perinatal lethality with severe defects in many organs and tissues. Although many substrates for these two ADAM proteases were identified over the last decade, the regulation of their surface appearance, their enzymatic activity and their substrate specificity are still not well understood. We therefore analyzed the constitutive and inducible surface expression of ADAM10 and ADAM17 on a variety of human T cell and tumor cell lines. We demonstrate that ADAM10 is constitutively present at comparably high levels on the majority of the tested cell types. Stimulation with phorbol ester and calcium ionophore does not significantly alter the amount of surface ADAM10, except for a slight down-regulation from T cell blasts. Using FasL shedding as a readout for ADAM10 activity, we show that PKC activation and calcium mobilization are both prerequisite for activation of ADAM10 resulting in a production of soluble FasL. In contrast to ADAM10, the close relative ADAM17 is detected at only low levels on unstimulated cells. ADAM17 surface expression on T cell blasts is rapidly induced by stimulation. Since this inducible mobilization of ADAM17 is sensitive to inhibitors of actin filament formation, we propose that ADAM17 but not ADAM10 is prestored in a subcellular compartment that is transported to the cell surface in an activation- and actin-dependent manner. Public Library of Science 2013-10-09 /pmc/articles/PMC3793918/ /pubmed/24130797 http://dx.doi.org/10.1371/journal.pone.0076853 Text en © 2013 Ebsen et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Ebsen, Henriette
Schröder, Alexandra
Kabelitz, Dieter
Janssen, Ottmar
Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title_full Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title_fullStr Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title_full_unstemmed Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title_short Differential Surface Expression of ADAM10 and ADAM17 on Human T Lymphocytes and Tumor Cells
title_sort differential surface expression of adam10 and adam17 on human t lymphocytes and tumor cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3793918/
https://www.ncbi.nlm.nih.gov/pubmed/24130797
http://dx.doi.org/10.1371/journal.pone.0076853
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