Negative regulation of Akt activity by p38α MAP kinase in cardiomyocytes involves membrane localization of PP2A through interaction with caveolin-1

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dc.contributor.authorZuluaga, Susana
dc.contributor.authorÁlvarez-Barrientos, Alberto
dc.contributor.authorGutiérrez Uzquiza, Álvaro
dc.contributor.authorBenito De Las Heras, Manuel R.
dc.contributor.authorNebreda, Angel R.
dc.contributor.authorPorras, Almudena
dc.contributor.authorPorras Gallo, María Almudena
dc.date.accessioned2024-01-12T10:20:06Z
dc.date.available2024-01-12T10:20:06Z
dc.date.issued2007-01-19
dc.description.abstractCardiomyocyte-derived cell lines deficient in p38α are more resistant to apoptosis owing to lower expression of the pro-apoptotic proteins Bax and Fas and upregulation of the ERK survival pathway. Here, we show that increased Akt activity also contributes to the enhanced survival of p38α-deficient cardiomyocytes. We found that the serine/threonine phosphatase PP2A can be targeted to caveolae through interaction with caveolin-1 in a p38α-dependent manner. In agreement with this, PP2A activity associated with caveolin-1 was higher in wild type than in p38α-deficient cells. Akt was also present in caveolae and incubation of wild-type cells with the PP2A inhibitor okadaic acid increases the levels of Akt activity. Thus, p38α-induced re-localization of PP2A to caveolae can lead to dephosphorylation and inhibition of Akt, which in turn would contribute to the decreased survival observed in wild type cells. However, cell detachment impairs the formation of the PP2A/caveolin-1 complex and, as a consequence, phospho-Akt levels and survival are no longer regulated by p38α in detached wild type cardiomyocytes. Our results suggest that p38α can negatively modulate Akt activity, independently of PI3K, by regulating the interaction between caveolin-1 and PP2A through a mechanism dependent on cell attachment.
dc.description.departmentDepto. de Bioquímica y Biología Molecular
dc.description.facultyFac. de Farmacia
dc.description.refereedTRUE
dc.description.sponsorshipComunidad Autónoma de Madrid
dc.description.sponsorshipFondo de Investigaciones Sanitarias
dc.description.sponsorshipMinisterio de Educación y Ciencia
dc.description.statuspub
dc.identifier.citationZuluaga S, Álvarez-Barrientos A, Gutiérrez-Uzquiza A, Benito M, Nebreda AR, Porras A. Negative regulation of Akt activity by p38α MAP kinase in cardiomyocytes involves membrane localization of PP2A through interaction with caveolin-1. Cellular Signalling 2007;19:62–74. https://doi.org/10.1016/j.cellsig.2006.05.032.
dc.identifier.doi10.1016/j.cellsig.2006.05.032
dc.identifier.issn0898-6568
dc.identifier.officialurlhttps://doi.org/10.1016/j.cellsig.2006.05.032
dc.identifier.pmid16844343
dc.identifier.urihttps://hdl.handle.net/20.500.14352/92712
dc.issue.number1
dc.journal.titleCellular Signalling
dc.language.isoeng
dc.page.final74
dc.page.initial62
dc.publisherElsevier
dc.relation.projectIDinfo:eu-repo/grantAgreement/CAM-08.4/0035/2001-10109
dc.relation.projectIDinfo:eu-repo/grantAgreement/PI041131
dc.rights.accessRightsrestricted access
dc.subject.cdu576.5
dc.subject.keywordp38MAPK
dc.subject.keywordPP2A
dc.subject.keywordCaveolin-1
dc.subject.keywordAkt
dc.subject.ucmBioquímica (Química)
dc.subject.unesco23 Química
dc.titleNegative regulation of Akt activity by p38α MAP kinase in cardiomyocytes involves membrane localization of PP2A through interaction with caveolin-1
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number19
dspace.entity.typePublication
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relation.isAuthorOfPublication6a240551-5797-4599-8d91-76bc38fecf8d
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relation.isAuthorOfPublication.latestForDiscoveryfe7d7e09-f48f-4104-b627-5f056790b029
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