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http://hdl.handle.net/10261/169371
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dc.contributor.author | Mendoza, Pilar | - |
dc.contributor.author | Martínez-Martín, Nuria | - |
dc.contributor.author | Bovolenta, Paola | - |
dc.contributor.author | Reyes-Garau, Diana | - |
dc.contributor.author | Hernansanz-Agustín, Pablo | - |
dc.contributor.author | Delgado, Pilar | - |
dc.contributor.author | Díaz-Muñoz, Manuel D. | - |
dc.contributor.author | Oeste, Clara L. | - |
dc.contributor.author | Fernández-Pisonero, Isabel | - |
dc.contributor.author | Castellano, Esther | - |
dc.contributor.author | Martínez-Ruiz, Antonio | - |
dc.contributor.author | Alonso-López, D. | - |
dc.contributor.author | Santos de Dios, Eugenio | - |
dc.contributor.author | Bustelo, Xosé R. | - |
dc.contributor.author | Kurosaki, Tomohiro | - |
dc.contributor.author | Alarcón, Balbino | - |
dc.date.accessioned | 2018-09-04T09:26:17Z | - |
dc.date.available | 2018-09-04T09:26:17Z | - |
dc.date.issued | 2018 | - |
dc.identifier | doi: 10.1126/scisignal.aal1506 | - |
dc.identifier | e-issn: 1937-9145 | - |
dc.identifier | issn: 1945-0877 | - |
dc.identifier.citation | Science Signaling 11(532): eaal1506 (2018) | - |
dc.identifier.uri | http://hdl.handle.net/10261/169371 | - |
dc.description.abstract | Upon antigen recognition within peripheral lymphoid organs, B cells interact with T cells and other immune cells to transiently form morphological structures called germinal centers (GCs), which are required for B cell clonal expansion, immunoglobulin class switching, and affinity maturation. This process, known as the GC response, is an energetically demanding process that requires the metabolic reprogramming of B cells. We showed that the Ras-related guanosine triphosphate hydrolase (GTPase) R-Ras2 (also known as TC21) plays an essential, nonredundant, and B cell–intrinsic role in the GC response. Both the conversion of B cells into GC B cells and their expansion were impaired in mice lacking R-Ras2, but not in those lacking a highly related R-Ras subfamily member or both the classic H-Ras and N-Ras GTPases. In the absence of R-Ras2, activated B cells did not exhibit increased oxidative phosphorylation or aerobic glycolysis. We showed that R-Ras2 was an effector of both the B cell receptor (BCR) and CD40 and that, in its absence, B cells exhibited impaired activation of the PI3K-Akt-mTORC1 pathway, reduced mitochondrial DNA replication, and decreased expression of genes involved in glucose metabolism. Because most human B cell lymphomas originate from GC B cells or B cells that have undergone the GC response, our data suggest that R-Ras2 may also regulate metabolism in B cell malignancies. | - |
dc.description.sponsorship | This work was supported by grants from the European Research Council ERC 2013–Advanced Grant 334763 NOVARIPP (to B.A.), the Ministerio de Economía y Competitividad [SAF2016-76394-R (to B.A.) and SAF2015-64556-R (to X.R.B.)], the Fondo de Investigaciones Sanitarias [FIS PI16/02137 (to E.S.)], the Instituto de Salud Carlos III RTICC [RD12/0036/0001 (to E.S.)], the Castilla-León Government [SA043U16 (to E.S.) and BIO/SA01/15, CSI049U16 (to X.R.B.)], the Worldwide Cancer Research [14-1248 (to X.R.B.)], the Fundación Ramón Areces, and the Fundación Científica de la Asociación Española Contra el Cáncer [GC16173472GARC (to B.A. and X.R.B.)]. | - |
dc.publisher | American Association for the Advancement of Science | - |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2016-76394-R | - |
dc.relation | info:eu-repo/grantAgreement/EC/FP7/334763 | - |
dc.relation | info:eu-repo/grantAgreement/MINECO/Plan Estatal de Investigación Científica y Técnica y de Innovación 2013-2016/SAF2015-64556-R | - |
dc.rights | closedAccess | - |
dc.title | R-Ras2 is required for germinal center formation to aid B cells during energetically demanding processes | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1126/scisignal.aal1506 | - |
dc.date.updated | 2018-09-04T09:26:17Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | European Research Council | - |
dc.contributor.funder | Ministerio de Economía y Competitividad (España) | - |
dc.contributor.funder | Instituto de Salud Carlos III | - |
dc.contributor.funder | Red Temática de Investigación Cooperativa en Cáncer (España) | - |
dc.contributor.funder | Junta de Castilla y León | - |
dc.contributor.funder | Worldwide Cancer Research | - |
dc.contributor.funder | Fundación Ramón Areces | - |
dc.contributor.funder | Fundación Científica Asociación Española Contra el Cáncer | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/100008054 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100007287 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100004587 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100003329 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100000781 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100002704 | es_ES |
dc.identifier.funder | http://dx.doi.org/10.13039/501100014180 | es_ES |
dc.identifier.pmid | 29844052 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.grantfulltext | none | - |
item.cerifentitytype | Publications | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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