Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yongjun, Tu, Yizeng, Zhao, Jianping, Chen, Ka, Wu, Chuanyue
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2009
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
_version_ 1782168468097859584
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
work_keys_str_mv AT zhangyongjun reversioninducedliminteractionwithsrcrevealsanovelsrcinactivationcycle
AT tuyizeng reversioninducedliminteractionwithsrcrevealsanovelsrcinactivationcycle
AT zhaojianping reversioninducedliminteractionwithsrcrevealsanovelsrcinactivationcycle
AT chenka reversioninducedliminteractionwithsrcrevealsanovelsrcinactivationcycle
AT wuchuanyue reversioninducedliminteractionwithsrcrevealsanovelsrcinactivationcycle