Mostrar el registro sencillo del ítem

dc.contributor.authorLodeiro Pose, María
dc.contributor.authorOTERO OTERO, BEGOÑA 
dc.contributor.authorSEOANE SUAREZ, CARLOS 
dc.contributor.authorBeiroa Tarrío, Daniel
dc.contributor.authorNogueiras Pozo, Rubén
dc.contributor.authorTheodoropoulou, Marily
dc.contributor.authorPardo Pérez, María 
dc.contributor.authorGallego, Rosalía
dc.contributor.authorPazos Randulfe, Yolanda 
dc.contributor.authorCasanueva Freijo, Felipe 
dc.contributor.authorPérez Camiña, Jesús 
dc.date.accessioned2017-06-07T07:21:45Z
dc.date.available2017-06-07T07:21:45Z
dc.date.issued2011
dc.identifier.issn1059-1524
dc.identifier.urihttp://hdl.handle.net/20.500.11940/5551
dc.description.abstractThe 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.isoeng
dc.titleThe SHP-1 protein tyrosine phosphatase negatively modulates Akt signaling in the ghrelin/GHSR1a system
dc.typeArtigoes
dc.authorsophosLodeiro, Maria
dc.authorsophosAlen, Begona O
dc.authorsophosMosteiro, Carlos S
dc.authorsophosBeiroa, Daniel
dc.authorsophosNogueiras, Ruben
dc.authorsophosTheodoropoulou, Marily
dc.authorsophosPardo, Maria
dc.authorsophosGallego, Rosalia
dc.authorsophosPazos, Yolanda
dc.authorsophosCasanueva, Felipe F
dc.authorsophosCamina, Jesus P
dc.identifier.doi10.1091/mbc.E11-04-0373
dc.identifier.isi296603300032
dc.identifier.pmid21900501
dc.identifier.sophos9903
dc.issue.number21
dc.journal.titleMOLECULAR BIOLOGY OF THE CELL
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago - Complexo Hospitalario Universitario de Santiago::Endocrinoloxía
dc.organizationServizo Galego de Saúde::Estrutura de Xestión Integrada (EOXI)::EOXI de Santiago::IDIS.- Instituto de investigaciones sanitarias de Santiago
dc.page.initial4182
dc.page.final4191
dc.rights.accessRightsopenAccess
dc.typesophosArtículo Original
dc.volume.number22


Ficheros en el ítem

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem