RT Journal Article
T1 Negative regulation of Akt activity by p38α MAP kinase in cardiomyocytes involves membrane localization of PP2A through interaction with caveolin-1
A1 Zuluaga, Susana
A1 Álvarez-Barrientos, Alberto
A1 Gutiérrez Uzquiza, Álvaro
A1 Benito De Las Heras, Manuel R.
A1 Nebreda, Angel R.
A1 Porras, Almudena
A1 Porras Gallo, María Almudena
AB Cardiomyocyte-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.
PB Elsevier
SN 0898-6568
YR 2007
FD 2007-01-19
LK https://hdl.handle.net/20.500.14352/92712
UL https://hdl.handle.net/20.500.14352/92712
LA eng
NO Zuluaga 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.
NO Comunidad Autónoma de Madrid
NO Fondo de Investigaciones Sanitarias
NO Ministerio de Educación y Ciencia
DS Docta Complutense
RD 1 jul 2024