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Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle
Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699145/ https://www.ncbi.nlm.nih.gov/pubmed/19307596 http://dx.doi.org/10.1083/jcb.200810155 |
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author | Zhang, Yongjun Tu, Yizeng Zhao, Jianping Chen, Ka Wu, Chuanyue |
author_facet | Zhang, Yongjun Tu, Yizeng Zhao, Jianping Chen, Ka Wu, Chuanyue |
author_sort | Zhang, Yongjun |
collection | PubMed |
description | Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1-dependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src inactivation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers. |
format | Text |
id | pubmed-2699145 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-26991452009-09-23 Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle Zhang, Yongjun Tu, Yizeng Zhao, Jianping Chen, Ka Wu, Chuanyue J Cell Biol Research Articles Aberrant Src activation plays prominent roles in cancer progression. However, how Src is activated in cancer cells is largely unknown. Genetic Src-activating mutations are rare and, therefore, are insufficient to account for Src activation commonly found in human cancers. In this study, we show that reversion-induced LIM (RIL), which is frequently lost in colon and other cancers as a result of epigenetic silencing, suppresses Src activation. Mechanistically, RIL suppresses Src activation through interacting with Src and PTPL1, allowing PTPL1-dependent dephosphorylation of Src at the activation loop. Importantly, the binding of RIL to Src is drastically reduced upon Src inactivation. Our results reveal a novel Src inactivation cycle in which RIL preferentially recognizes active Src and facilitates PTPL1-mediated inactivation of Src. Inactivation of Src, in turn, promotes dissociation of RIL from Src, allowing the initiation of a new Src inactivation cycle. Epigenetic silencing of RIL breaks this Src inactivation cycle and thereby contributes to aberrant Src activation in human cancers. The Rockefeller University Press 2009-03-23 /pmc/articles/PMC2699145/ /pubmed/19307596 http://dx.doi.org/10.1083/jcb.200810155 Text en © 2009 Zhang 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.jcb.org/misc/terms.shtml). 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 Zhang, Yongjun Tu, Yizeng Zhao, Jianping Chen, Ka Wu, Chuanyue Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title | Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title_full | Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title_fullStr | Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title_full_unstemmed | Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title_short | Reversion-induced LIM interaction with Src reveals a novel Src inactivation cycle |
title_sort | reversion-induced lim interaction with src reveals a novel src inactivation cycle |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2699145/ https://www.ncbi.nlm.nih.gov/pubmed/19307596 http://dx.doi.org/10.1083/jcb.200810155 |
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