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http://hdl.handle.net/10261/115426
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dc.contributor.author | Barceló, Carlos | - |
dc.contributor.author | Paco, Noelia | - |
dc.contributor.author | Morell, Mireia | - |
dc.contributor.author | Álvarez-Moya, Blanca | - |
dc.contributor.author | Bota-Rabassedas, Neus | - |
dc.contributor.author | Jaumot, Montserrat | - |
dc.contributor.author | Vilardell, Felip | - |
dc.contributor.author | Capellá, Gabriel | - |
dc.contributor.author | Agell, Neus | - |
dc.date.accessioned | 2015-05-19T12:42:17Z | - |
dc.date.available | 2015-05-19T12:42:17Z | - |
dc.date.issued | 2014-02-15 | - |
dc.identifier | doi: 10.1158/0008-5472.CAN-13-1750 | - |
dc.identifier | issn: 0008-5472 | - |
dc.identifier | e-issn: 1538-7445 | - |
dc.identifier.citation | Cancer Research 74: 1190-1199 (2014) | - |
dc.identifier.uri | http://hdl.handle.net/10261/115426 | - |
dc.description.abstract | KRAS phosphorylation has been reported recently to modulate the activity of mutant KRAS protein in vitro. In this study, we defined S181 as a specific phosphorylation site required to license the oncogenic function of mutant KRAS in vivo. The phosphomutant S181A failed to induce tumors in mice, whereas the phosphomimetic mutant S181D exhibited an enhanced tumor formation capacity, compared with the wild-type KRAS protein. Reduced growth of tumors composed of cells expressing the nonphosphorylatable KRAS S181A mutant was correlated with increased apoptosis. Conversely, increased growth of tumors composed of cells expressing the phosphomimetic KRAS S181D mutant was correlated with increased activation of AKT and ERK, two major downstream effectors of KRAS. Pharmacologic treatment with PKC inhibitors impaired tumor growth associated with reduced levels of phosphorylated KRAS and reduced effector activation. In a panel of human tumor cell lines expressing various KRAS isoforms, we showed that KRAS phosphorylation was essential for survival and tumorigenic activity. Furthermore, we identified phosphorylated KRAS in a panel of primary human pancreatic tumors. Taken together, our findings establish that KRAS requires S181 phosphorylation to manifest its oncogenic properties, implying that its inhibition represents a relevant target to attack KRAS-driven tumors. © 2014 American Association for Cancer Research. | - |
dc.description.sponsorship | This study was supported by MICINN-Spain (SAF2010-20712) and RTICC (MINECO-Spain; groups RD 12/0036/0049 and RD 12/0036/0008). C. Barceló and N. Paco are recipients of predoctoral fellowships from MEC-Spain and the Catalan Government, respectively. | - |
dc.description.sponsorship | http://dx.doi.org/10.1158/0008-5472.CAN-13-1750 | - |
dc.publisher | American Association for Cancer Research | - |
dc.rights | closedAccess | - |
dc.title | Phosphorylation at ser-181 of oncogenic KRAS is required for tumor growth | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1158/0008-5472.CAN-13-1750 | - |
dc.date.updated | 2015-05-19T12:42:17Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | Ministerio de Ciencia e Innovación (España) | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | Ministerio de Educación y Ciencia (España) | - |
dc.contributor.funder | Generalitat de Catalunya | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004837 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100002809 | es_ES |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
item.cerifentitytype | Publications | - |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
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