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The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system
dc.contributor.author | Lodeiro Pose, María | |
dc.contributor.author | OTERO OTERO, BEGOÑA | |
dc.contributor.author | SEOANE SUAREZ, CARLOS | |
dc.contributor.author | Beiroa Tarrío, Daniel | |
dc.contributor.author | Nogueiras Pozo, Rubén | |
dc.contributor.author | Theodoropoulou, Marily | |
dc.contributor.author | Pardo Pérez, María | |
dc.contributor.author | Gallego, Rosalía | |
dc.contributor.author | Pazos Randulfe, Yolanda | |
dc.contributor.author | Casanueva Freijo, Felipe | |
dc.contributor.author | Pérez Camiña, Jesús | |
dc.date.accessioned | 2017-06-07T07:21:45Z | |
dc.date.available | 2017-06-07T07:21:45Z | |
dc.date.issued | 2011 | |
dc.identifier.issn | 1059-1524 | |
dc.identifier.uri | http://hdl.handle.net/20.500.11940/5551 | |
dc.description.abstract | The aim of the present study was to identify the signaling mechanism(s) responsible for the modulation of growth hormone secretagogue receptor type 1a (GHSR1a)-associated Akt activity. Ghrelin leads to the activation of Akt through the interplay of distinct signaling mechanisms: an early G(i/o) protein-dependent pathway and a late pathway mediated by beta-arrestins. We found that the Src homology 2-containing protein tyrosine phosphatase (SHP-1) was an essential molecule in both G(i/o) protein-dependent and beta-arrestin-mediated pathways. More specifically, the role of SHP-1 in the G(i/o) protein-dependent pathway was demonstrated by the fact that the overexpression of a catalytically defective SHP-1 augments tyrosine phosphorylation of the PI3K regulatory subunit p85, leading to an increase in the phosphorylation of cSrc and phosphoinositide-dependent protein kinase 1, and finally activating Akt. The presence of SHP-1 in the beta-arrestin-scaffolded complex and its attenuating effect on the cSrc and Akt activities verified that SHP-1 regulates not only the G(i/o) protein-dependent pathway but also the beta-arrestin-mediated pathway. Assays performed in preadipocyte and adipocyte 3T3-L1 cells showed SHP-1 expression. According to our results in HEK-GHSR1a cells, ghrelin stimulated SHP-1 phosphorylation in 3T3-L1 cells. The increase in ghrelin-induced Akt activity was enhanced by small interfering RNA of SHP-1 in preadipocyte 3T3-L1 cells. These results were reproduced in white adipose tissue obtained from mice, in which SHP-1 exhibited higher expression in omental than in subcutaneous tissue. Furthermore, this pattern of expression was inverted in mice fed a high-fat diet, suggesting a role for SHP-1 in controlling ghrelin sensitivity in adipose tissue. Indeed, SHP-1 deficiency was associated with augmented ghrelin-evoked Akt phosphorylation in omental tissue, as well as decreased phosphorylation under overexpression of SHP-1 in subcutaneous tissue. These findings showed a novel role for SHP-1 in the regulation of Akt activity through the modulation of the ghrelin/GHSR1a system signaling. | |
dc.language.iso | eng | |
dc.title | The SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system | |
dc.type | Artigo | es |
dc.authorsophos | Lodeiro, Maria | |
dc.authorsophos | Alen, Begona O | |
dc.authorsophos | Mosteiro, Carlos S | |
dc.authorsophos | Beiroa, Daniel | |
dc.authorsophos | Nogueiras, Ruben | |
dc.authorsophos | Theodoropoulou, Marily | |
dc.authorsophos | Pardo, Maria | |
dc.authorsophos | Gallego, Rosalia | |
dc.authorsophos | Pazos, Yolanda | |
dc.authorsophos | Casanueva, Felipe F | |
dc.authorsophos | Camina, Jesus P | |
dc.identifier.doi | 10.1091/mbc.E11-04-0373 | |
dc.identifier.isi | 296603300032 | |
dc.identifier.pmid | 21900501 | |
dc.identifier.sophos | 9903 | |
dc.issue.number | 21 | |
dc.journal.title | MOLECULAR BIOLOGY OF THE CELL | |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Endocrinoloxía | |
dc.organization | Servizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago | |
dc.page.initial | 4182 | |
dc.page.final | 4191 | |
dc.rights.accessRights | openAccess | |
dc.typesophos | Artículo Original | |
dc.volume.number | 22 |