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Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation

CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca(2+) influx or the activation of protein kinase C. Here we show that CD44-mediate...

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Autores principales: Nagano, Osamu, Murakami, Daizo, Hartmann, Dieter, de Strooper, Bart, Saftig, Paul, Iwatsubo, Takeshi, Nakajima, Motowo, Shinohara, Masanori, Saya, Hideyuki
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2004
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172408/
https://www.ncbi.nlm.nih.gov/pubmed/15197174
http://dx.doi.org/10.1083/jcb.200310024
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author Nagano, Osamu
Murakami, Daizo
Hartmann, Dieter
de Strooper, Bart
Saftig, Paul
Iwatsubo, Takeshi
Nakajima, Motowo
Shinohara, Masanori
Saya, Hideyuki
author_facet Nagano, Osamu
Murakami, Daizo
Hartmann, Dieter
de Strooper, Bart
Saftig, Paul
Iwatsubo, Takeshi
Nakajima, Motowo
Shinohara, Masanori
Saya, Hideyuki
author_sort Nagano, Osamu
collection PubMed
description CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca(2+) influx or the activation of protein kinase C. Here we show that CD44-mediated cell–matrix adhesion is terminated by two independent ADAM family metalloproteinases, ADAM10 and ADAM17, differentially regulated in response to those stimuli. Ca(2+) influx activates ADAM10 by regulating the association between calmodulin and ADAM10, leading to CD44 ectodomain cleavage. Depletion of ADAM10 strongly inhibits the Ca(2+) influx-induced cell detachment from matrix. On the other hand, phorbol ester stimulation activates ADAM17 through the activation of PKC and small GTPase Rac, inducing proteolysis of CD44. Furthermore, depletion of ADAM10 or ADAM17 markedly suppressed CD44-dependent cancer cell migration on HA, but not on fibronectin. The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell–matrix interaction and cell migration.
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spelling pubmed-21724082008-03-05 Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation Nagano, Osamu Murakami, Daizo Hartmann, Dieter de Strooper, Bart Saftig, Paul Iwatsubo, Takeshi Nakajima, Motowo Shinohara, Masanori Saya, Hideyuki J Cell Biol Article CD44 is an adhesion molecule that interacts with hyaluronic acid (HA) and undergoes sequential proteolytic cleavages in its ectodomain and intramembranous domain. The ectodomain cleavage is triggered by extracellular Ca(2+) influx or the activation of protein kinase C. Here we show that CD44-mediated cell–matrix adhesion is terminated by two independent ADAM family metalloproteinases, ADAM10 and ADAM17, differentially regulated in response to those stimuli. Ca(2+) influx activates ADAM10 by regulating the association between calmodulin and ADAM10, leading to CD44 ectodomain cleavage. Depletion of ADAM10 strongly inhibits the Ca(2+) influx-induced cell detachment from matrix. On the other hand, phorbol ester stimulation activates ADAM17 through the activation of PKC and small GTPase Rac, inducing proteolysis of CD44. Furthermore, depletion of ADAM10 or ADAM17 markedly suppressed CD44-dependent cancer cell migration on HA, but not on fibronectin. The spatio-temporal regulation of two independent signaling pathways for CD44 cleavage plays a crucial role in cell–matrix interaction and cell migration. The Rockefeller University Press 2004-06-21 /pmc/articles/PMC2172408/ /pubmed/15197174 http://dx.doi.org/10.1083/jcb.200310024 Text en Copyright © 2004, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Article
Nagano, Osamu
Murakami, Daizo
Hartmann, Dieter
de Strooper, Bart
Saftig, Paul
Iwatsubo, Takeshi
Nakajima, Motowo
Shinohara, Masanori
Saya, Hideyuki
Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title_full Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title_fullStr Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title_full_unstemmed Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title_short Cell–matrix interaction via CD44 is independently regulated by different metalloproteinases activated in response to extracellular Ca(2+) influx and PKC activation
title_sort cell–matrix interaction via cd44 is independently regulated by different metalloproteinases activated in response to extracellular ca(2+) influx and pkc activation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2172408/
https://www.ncbi.nlm.nih.gov/pubmed/15197174
http://dx.doi.org/10.1083/jcb.200310024
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