Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism
c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 do...
| Autores: | , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universidad de Barcelona |
| Repositorio: | Dipòsit Digital de la UB |
| OAI Identifier: | oai:diposit.ub.edu:2445/44749 |
| Acceso en línea: | https://hdl.handle.net/2445/44749 |
| Access Level: | acceso abierto |
| Palabra clave: | Proteïnes quinases Lípids Receptors cel·lulars Regulació cel·lular Lligands (Bioquímica) Protein kinases Lipids Cell receptors Cellular control mechanisms Ligands (Biochemistry) |
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Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanismPérez, YolandaMattei, MarianoIgea, AnaAmata, IreneGairí Tahull, MargaridaNebreda, Àngel R.Bernadó Peretó, PauPons Vallès, MiquelProteïnes quinasesLípidsReceptors cel·lularsRegulació cel·lularLligands (Bioquímica)Protein kinasesLipidsCell receptorsCellular control mechanismsLigands (Biochemistry)c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation.Nature Publishing Group2013info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://hdl.handle.net/2445/44749Articles publicats en revistes (Química Inorgànica i Orgànica)reponame:Dipòsit Digital de la UBinstname:Universidad de BarcelonaInglésinfo:eu-repo/semantics/altIdentifier/doi/10.1038/srep0129Reproducció del document publicat a: http://dx.doi.org/10.1038/srep0129Scientific Reports, 2013, vol. 3, num. 1295http://dx.doi.org/10.1038/srep0129info:eu-repo/grantAgreement/EC/FP7/261863cc-by-nc-nd (c) Pérez, Yolanda et al., 2013http://creativecommons.org/licenses/by-nc-nd/3.0/esinfo:eu-repo/semantics/openAccessoai:diposit.ub.edu:2445/447492026-05-27T06:46:51Z |
| dc.title.none.fl_str_mv |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| title |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| spellingShingle |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism Pérez, Yolanda Proteïnes quinases Lípids Receptors cel·lulars Regulació cel·lular Lligands (Bioquímica) Protein kinases Lipids Cell receptors Cellular control mechanisms Ligands (Biochemistry) |
| title_short |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| title_full |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| title_fullStr |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| title_full_unstemmed |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| title_sort |
Lipid binding by the unique and SH3 domains of c-Src suggests a new regulation mechanism |
| dc.creator.none.fl_str_mv |
Pérez, Yolanda Mattei, Mariano Igea, Ana Amata, Irene Gairí Tahull, Margarida Nebreda, Àngel R. Bernadó Peretó, Pau Pons Vallès, Miquel |
| author |
Pérez, Yolanda |
| author_facet |
Pérez, Yolanda Mattei, Mariano Igea, Ana Amata, Irene Gairí Tahull, Margarida Nebreda, Àngel R. Bernadó Peretó, Pau Pons Vallès, Miquel |
| author_role |
author |
| author2 |
Mattei, Mariano Igea, Ana Amata, Irene Gairí Tahull, Margarida Nebreda, Àngel R. Bernadó Peretó, Pau Pons Vallès, Miquel |
| author2_role |
author author author author author author author |
| dc.subject.none.fl_str_mv |
Proteïnes quinases Lípids Receptors cel·lulars Regulació cel·lular Lligands (Bioquímica) Protein kinases Lipids Cell receptors Cellular control mechanisms Ligands (Biochemistry) |
| topic |
Proteïnes quinases Lípids Receptors cel·lulars Regulació cel·lular Lligands (Bioquímica) Protein kinases Lipids Cell receptors Cellular control mechanisms Ligands (Biochemistry) |
| description |
c-Src is a non-receptor tyrosine kinase involved in numerous signal transduction pathways. The kinase,SH3 and SH2 domains of c-Src are attached to the membrane-anchoring SH4 domain through the flexible Unique domain. Here we show intra- and intermolecular interactions involving the Unique and SH3 domains suggesting the presence of a previously unrecognized additional regulation layer in c-Src. We have characterized lipid binding by the Unique and SH3 domains, their intramolecular interaction and its allosteric modulation by a SH3-binding peptide or by Calcium-loaded calmodulin binding to the Unique domain. We also show reduced lipid binding following phosphorylation at conserved sites of the Unique domain. Finally, we show that injection of full-length c-Src with mutations that abolish lipid binding by the Unique domain causes a strong in vivo phenotype distinct from that of wild-type c-Src in a Xenopus oocyte model system, confirming the functional role of the Unique domain in c-Src regulation. |
| publishDate |
2013 |
| dc.date.none.fl_str_mv |
2013 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
https://hdl.handle.net/2445/44749 |
| url |
https://hdl.handle.net/2445/44749 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/doi/10.1038/srep0129 Reproducció del document publicat a: http://dx.doi.org/10.1038/srep0129 Scientific Reports, 2013, vol. 3, num. 1295 http://dx.doi.org/10.1038/srep0129 info:eu-repo/grantAgreement/EC/FP7/261863 |
| dc.rights.none.fl_str_mv |
cc-by-nc-nd (c) Pérez, Yolanda et al., 2013 http://creativecommons.org/licenses/by-nc-nd/3.0/es info:eu-repo/semantics/openAccess |
| rights_invalid_str_mv |
cc-by-nc-nd (c) Pérez, Yolanda et al., 2013 http://creativecommons.org/licenses/by-nc-nd/3.0/es |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
application/pdf |
| dc.publisher.none.fl_str_mv |
Nature Publishing Group |
| publisher.none.fl_str_mv |
Nature Publishing Group |
| dc.source.none.fl_str_mv |
Articles publicats en revistes (Química Inorgànica i Orgànica) reponame:Dipòsit Digital de la UB instname:Universidad de Barcelona |
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Universidad de Barcelona |
| reponame_str |
Dipòsit Digital de la UB |
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Dipòsit Digital de la UB |
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|
| repository.mail.fl_str_mv |
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1869403917245218816 |
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15.300724 |