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Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors
Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue patterning during normal and oncogenic development, in which unscheduled expression and somatic mutations contribute to tumor progression. EphA and B subtypes preferentially bind A- and B-type ephrins, respectively, re...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241718/ https://www.ncbi.nlm.nih.gov/pubmed/22144690 http://dx.doi.org/10.1083/jcb.201104037 |
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author | Janes, Peter W. Griesshaber, Bettina Atapattu, Lakmali Nievergall, Eva Hii, Linda L. Mensinga, Anneloes Chheang, Chanly Day, Bryan W. Boyd, Andrew W. Bastiaens, Philippe I. Jørgensen, Claus Pawson, Tony Lackmann, Martin |
author_facet | Janes, Peter W. Griesshaber, Bettina Atapattu, Lakmali Nievergall, Eva Hii, Linda L. Mensinga, Anneloes Chheang, Chanly Day, Bryan W. Boyd, Andrew W. Bastiaens, Philippe I. Jørgensen, Claus Pawson, Tony Lackmann, Martin |
author_sort | Janes, Peter W. |
collection | PubMed |
description | Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue patterning during normal and oncogenic development, in which unscheduled expression and somatic mutations contribute to tumor progression. EphA and B subtypes preferentially bind A- and B-type ephrins, respectively, resulting in receptor complexes that propagate via homotypic Eph–Eph interactions. We now show that EphA and B receptors cocluster, such that specific ligation of one receptor promotes recruitment and cross-activation of the other. Remarkably, coexpression of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross-activation or cross-inhibition, depending on relative expression. Our findings indicate that cellular responses to ephrin contact are determined by the EphA/EphB receptor profile on a given cell rather than the individual Eph subclass. Importantly, they imply that in tumor cells coexpressing different Ephs, functional mutations in one subtype may cause phenotypes that are a result of altered signaling from heterotypic rather from homotypic Eph clusters. |
format | Online Article Text |
id | pubmed-3241718 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-32417182012-06-12 Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors Janes, Peter W. Griesshaber, Bettina Atapattu, Lakmali Nievergall, Eva Hii, Linda L. Mensinga, Anneloes Chheang, Chanly Day, Bryan W. Boyd, Andrew W. Bastiaens, Philippe I. Jørgensen, Claus Pawson, Tony Lackmann, Martin J Cell Biol Research Articles Eph receptors interact with ephrin ligands on adjacent cells to facilitate tissue patterning during normal and oncogenic development, in which unscheduled expression and somatic mutations contribute to tumor progression. EphA and B subtypes preferentially bind A- and B-type ephrins, respectively, resulting in receptor complexes that propagate via homotypic Eph–Eph interactions. We now show that EphA and B receptors cocluster, such that specific ligation of one receptor promotes recruitment and cross-activation of the other. Remarkably, coexpression of a kinase-inactive mutant EphA3 with wild-type EphB2 can cause either cross-activation or cross-inhibition, depending on relative expression. Our findings indicate that cellular responses to ephrin contact are determined by the EphA/EphB receptor profile on a given cell rather than the individual Eph subclass. Importantly, they imply that in tumor cells coexpressing different Ephs, functional mutations in one subtype may cause phenotypes that are a result of altered signaling from heterotypic rather from homotypic Eph clusters. The Rockefeller University Press 2011-12-12 /pmc/articles/PMC3241718/ /pubmed/22144690 http://dx.doi.org/10.1083/jcb.201104037 Text en © 2011 Janes et al. 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 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Janes, Peter W. Griesshaber, Bettina Atapattu, Lakmali Nievergall, Eva Hii, Linda L. Mensinga, Anneloes Chheang, Chanly Day, Bryan W. Boyd, Andrew W. Bastiaens, Philippe I. Jørgensen, Claus Pawson, Tony Lackmann, Martin Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title | Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title_full | Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title_fullStr | Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title_full_unstemmed | Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title_short | Eph receptor function is modulated by heterooligomerization of A and B type Eph receptors |
title_sort | eph receptor function is modulated by heterooligomerization of a and b type eph receptors |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241718/ https://www.ncbi.nlm.nih.gov/pubmed/22144690 http://dx.doi.org/10.1083/jcb.201104037 |
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