Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src
Data Availability Statement: All data are included within the manuscript. Funding: This work was funded by grants to AV from the Secretaría de Estado de Investigación, Desarrollo e Innovación (SAF2011-23494 & SAF2014-52048-R), the Consejería de Educación de la Comunidad de Madrid (S2011/BMD-2349), t...
محفوظ في:
| منشور في: |
2015
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| الموضوعات: | |
| الوصول للمادة أونلاين: | http://hdl.handle.net/10872/15702 |
| الوسوم: |
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| bitstream.checksumAlgorithm.fl_str_mv | MD5 MD5 |
| bitstream.url.fl_str_mv | https://saber.ucv.ve/jspui/bitstream/10872/15702/1/Stateva%20et%20al%20%20PLOs%20One%202015%20Src-CaM.pdf https://saber.ucv.ve/jspui/bitstream/10872/15702/2/license.txt |
| dc.contributor.author.none.fl_str_mv | Stateva, Silviya R. Salas, Valentina Anguita, Estefanía Benaím, Gustavo Villalobo, Antonio |
| dc.creator.fl_str_mv | Stateva, Silviya R. Salas, Valentina Anguita, Estefanía Benaím, Gustavo Villalobo, Antonio |
| dc.date.accessioned.none.fl_str_mv | 2017-04-25T15:47:56Z |
| dc.date.available.none.fl_str_mv | 2017-04-25T15:47:56Z |
| dc.date.issued.none.fl_str_mv | 2015 |
| dc.identifier.issn.none.fl_str_mv | 1932-6203 (Electronic) DOI:10.1371/journal.pone.0128783 |
| dc.identifier.uri.none.fl_str_mv | http://hdl.handle.net/10872/15702 |
| dc.language.iso.en_US.fl_str_mv | en |
| dc.publisher.en_US.fl_str_mv | PLOS ONE |
| dc.relation.ispartofseries.none.fl_str_mv | Vol. 10;No. 6 |
| dc.subject.en_US.fl_str_mv | Ca2+/Calmodulin Apo-Calmodulin Tyrosine Kinase Activity of c-Src cellular processes solid tumors |
| dc.title.en_US.fl_str_mv | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| dc.type.en_US.fl_str_mv | Article |
| description | Data Availability Statement: All data are included within the manuscript. Funding: This work was funded by grants to AV from the Secretaría de Estado de Investigación, Desarrollo e Innovación (SAF2011-23494 & SAF2014-52048-R), the Consejería de Educación de la Comunidad de Madrid (S2011/BMD-2349), the CSIC program i- COOP+ 2014 (COOPA20053), and the European Commission (contract PITN-GA-2011-289033). SRS received funding from the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7/2007-2013 under REA grant agreement n° PITN-GA-2011-289033. VS and GB were supported by fellowship and grants from the Consejo de Desarrollo Científico y Humanístico de la Universidad Central de Venezuela (03-00-6057-2005 & PG-03-8728-2013) and Fondo Nacional de Ciencia, Tecnología e Innovación (P-2011000884). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. |
| id | SABERUCV_d97757384d4f7876cf4697cff92df18c |
| identifier_str_mv | 1932-6203 (Electronic) DOI:10.1371/journal.pone.0128783 |
| language_invalid_str_mv | en |
| network_acronym_str | SABERUCV |
| network_name_str | Repositorio Institucional de la Universidad Central de Venezuela |
| oai_identifier_str | oai:saber.ucv.ve:10872/15702 |
| publishDate | 2015 |
| publishDateSort | 2015 |
| repository.mail.fl_str_mv | sfwrussians@gmail.com |
| repository.name.fl_str_mv | Saber UCV |
| repository_id_str | |
| spelling | Stateva, Silviya R.Salas, ValentinaAnguita, EstefaníaBenaím, GustavoVillalobo, Antonio2017-04-25T15:47:56Z2017-04-25T15:47:56Z20151932-6203 (Electronic)DOI:10.1371/journal.pone.0128783http://hdl.handle.net/10872/15702Data Availability Statement: All data are included within the manuscript. Funding: This work was funded by grants to AV from the Secretaría de Estado de Investigación, Desarrollo e Innovación (SAF2011-23494 & SAF2014-52048-R), the Consejería de Educación de la Comunidad de Madrid (S2011/BMD-2349), the CSIC program i- COOP+ 2014 (COOPA20053), and the European Commission (contract PITN-GA-2011-289033). SRS received funding from the People Program (Marie Curie Actions) of the European Union's Seventh Framework Program FP7/2007-2013 under REA grant agreement n° PITN-GA-2011-289033. VS and GB were supported by fellowship and grants from the Consejo de Desarrollo Científico y Humanístico de la Universidad Central de Venezuela (03-00-6057-2005 & PG-03-8728-2013) and Fondo Nacional de Ciencia, Tecnología e Innovación (P-2011000884). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist.Src family non-receptor tyrosine kinases play a prominent role in multiple cellular processes, including: cell proliferation, differentiation, cell survival, stress response, and cell adhesion and migration, among others. And when deregulated by mutations, overexpression, and/or the arrival of faulty incoming signals, its hyperactivity contributes to the development of hematological and solid tumors. c-Src is a prototypical member of this family of kinases, which is highly regulated by a set of phosphorylation events. Other factor contributing to the regulation of Src activity appears to be mediated by the Ca2+ signal generated in cells by different effectors, where the Ca2+-receptor protein calmodulin (CaM) plays a key role. In this report we demonstrate that CaM directly interacts with Src in both Ca2+-dependent and Ca2 +-independent manners in vitro and in living cells, and that the CaM antagonist N-(6-aminohexyl)- 5-chloro-1-naphthalenesulfonamide (W-7) inhibits the activation of this kinase induced by the upstream activation of the epidermal growth factor receptor (EGFR), in human carcinoma epidermoide A431 cells, and by hydrogen peroxide-induced oxidative stress, in both A431 cells and human breast adenocarcinoma SK-BR-3 cells. Furthermore, we show that the Ca2+/CaM complex strongly activates the auto-phosphorylation and tyrosine kinase activity of c-Src toward exogenous substrates, but most relevantly and for the first time, we demonstrate that Ca2+-free CaM (apo-CaM) exerts a far higher activatory action on Src auto-phosphorylation and kinase activity toward exogenous substrates than the one exerted by the Ca2+/CaM complex. This suggests that a transient increase in the cytosolic concentration of free Ca2+ is not an absolute requirement for CaM-mediated activation of Src in living cells, and that a direct regulation of Src by apo-CaM could be inferred.enPLOS ONEVol. 10;No. 6Ca2+/CalmodulinApo-CalmodulinTyrosine KinaseActivity of c-Srccellular processessolid tumorsCa2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-SrcArticleORIGINALStateva et al PLOs One 2015 Src-CaM.pdfStateva et al PLOs One 2015 Src-CaM.pdfapplication/pdf2228467https://saber.ucv.ve/jspui/bitstream/10872/15702/1/Stateva%20et%20al%20%20PLOs%20One%202015%20Src-CaM.pdf9d9a0281ae8b090bd3fcac4ab2bf93e9MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81509https://saber.ucv.ve/jspui/bitstream/10872/15702/2/license.txt7c020282d630887ba819753d2e4a4c58MD5210872/15702oai:saber.ucv.ve:10872/157022017-04-25 19:08:35.677Saber UCVsfwrussians@gmail.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 |
| spellingShingle | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src Ca2+/Calmodulin Apo-Calmodulin Tyrosine Kinase Activity of c-Src cellular processes solid tumors |
| title | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| title_full | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| title_fullStr | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| title_full_unstemmed | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| title_short | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| title_sort | Ca2+/Calmodulin and Apo-Calmodulin Both Bind to and Enhance the Tyrosine Kinase Activity of c-Src |
| topic | Ca2+/Calmodulin Apo-Calmodulin Tyrosine Kinase Activity of c-Src cellular processes solid tumors |
| url | http://hdl.handle.net/10872/15702 |