Person: Porras Gallo, María Almudena
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First Name
María Almudena
Last Name
Porras Gallo
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Farmacia
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
3 results
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Item Negative regulation of Akt activity by p38α MAP kinase in cardiomyocytes involves membrane localization of PP2A through interaction with caveolin-1(Cellular Signalling, 2007) Zuluaga, Susana; Álvarez-Barrientos, Alberto; Gutiérrez Uzquiza, Álvaro; Benito De Las Heras, Manuel R.; Nebreda, Angel R.; Porras, Almudena; Porras Gallo, María AlmudenaCardiomyocyte-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.Item p38alpha MAPK can positively or negatively regulate Rac-1 activity depending on the presence of serum(FEBS Letters, 2007) Zuluaga, Susana; Gutiérrez Uzquiza, Álvaro; Bragado, Paloma; Alvarez-Barrientos, Alberto; Benito De Las Heras, Manuel R.; Nebreda, Angel R; Porras Gallo, María AlmudenaThe small GTP-ase Rac-1 can trigger p38 MAPK activation and, in turn, p38alpha can regulate signalling pathways that potentially impinge on Rac-1 activity. We have investigated the cross-talk between p38alpha and Rac-1 and found that p38alpha regulates the association between Rac-1 and caveolin-1 in serum-deprived cardiomyocytes. This interaction depends on cell attachment and correlates with higher levels of active Rac-1. Actin organization might regulate the formation of Rac-1-caveolin-1 complexes. In contrast, the Rac-1-caveolin-1 interaction is almost undetectable in the presence of serum, where Rac-1 activity is negatively regulated by p38alpha. Our results indicate that p38alpha can differentially contribute to Rac-1 activation depending on the presence of serum.Item C3G down-regulates p38 MAPK activity in response to stress by Rap-1 independent mechanisms: Involvement in cell death(Cellular Signalling, 2010) Gutiérrez Uzquiza, Álvaro; Arechederra, María; Molina, Isabel; Baños, Rocío; Maia, Vera; Benito De Las Heras, Manuel R.; Guerrero, Carmen; Porras Gallo, María AlmudenaWe present here evidences supporting a negative regulation of p38α MAPK activity by C3G in MEFs triggered by stress, which can mediate cell death or survival depending on the stimuli. Upon serum deprivation, C3G induces survival through inhibition of p38α activation, which mediates apoptosis. In contrast, in response to H2O2, C3G behaves as a pro-apoptotic molecule, as its knock-down or knock-out enhances survival through up-regulation of p38α activation, which plays an anti-apoptotic role under these conditions. Moreover, the C3G target, Rap-1, plays an opposite role, also through regulation of p38α MAPK activity. Our data also suggest that changes in the protein levels of some members of the Bcl-2 family could account for the regulation of cell death by C3G and/or Rap-1 through p38α MAPK. Bim/Bcl-xL ratio appears to be important in the regulation of cell survival, both upon serum deprivation and in response to H2O2. In addition, the increase in BNIP-3 levels induced by C3G knock-down in wt cells treated with H2O2 might play a role preventing cell death. Therefore, we can conclude that C3G is a negative regulator of p38α MAPK in MEFs, while Rap-1 is a positive regulator, but both, through the regulation of p38α activity, can promote cell survival or cell death depending on the stimuli.