Cargando…
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...
Autores principales: | , , , , , , , , |
---|---|
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 |
_version_ | 1782145056626442240 |
---|---|
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. |
format | Text |
id | pubmed-2172408 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2004 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT naganoosamu cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT murakamidaizo cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT hartmanndieter cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT destrooperbart cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT saftigpaul cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT iwatsubotakeshi cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT nakajimamotowo cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT shinoharamasanori cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation AT sayahideyuki cellmatrixinteractionviacd44isindependentlyregulatedbydifferentmetalloproteinasesactivatedinresponsetoextracellularca2influxandpkcactivation |