Details

Autor(en) / Beteiligte

• Gervais, Marianne
• Dugourd, Céline
• Muller, Laurent
• Ardidie, Corinne
• Canton, Brigitte
• Loviconi, Laetitia
• Corvol, Pierre
• Chneiweiss, Hervé
• Monnot, Catherine
• York, John

Titel

Akt down-regulates ERK1/2 nuclear localization and angiotensin II-induced cell proliferation through PEA-15

Ist Teil von

• Molecular biology of the cell, 2006-09, Vol.17 (9), p.3940-3951

Ort / Verlag

United States: American Society for Cell Biology

Erscheinungsjahr

2006

Quelle

MEDLINE

Beschreibungen/Notizen

• Angiotensin II (AngII) type 1 receptors (AT1) regulate cell growth through the extracellular signal-regulated kinase (ERK)1/2 and phosphatidylinositol 3-kinase (PI3K) pathways. ERK1/2 and Akt/protein kinase B, downstream of PI3K, are independently activated but both required for mediating AngII-induced proliferation when expressed at endogenous levels. We investigate the effect of an increase in the expression of wild-type Akt1 by using Chinese hamster ovary (CHO)-AT1 cells. Unexpectedly, Akt overexpression inhibits the AT1-mediated proliferation. This effect could be generated by a cross-talk between the PI3K and ERK1/2 pathways. A functional partner is the phosphoprotein enriched in astrocytes of 15 kDa (PEA-15), an Akt substrate known to bind ERK1/2 and to regulate their nuclear translocation. We report that Akt binds to PEA-15 and that Akt activation leads to PEA-15 stabilization, independently of PEA-15 interaction with ERK1/2. Akt cross-talk with PEA-15 does not affect ERK1/2 activation but decreases their nuclear activity as a result of the blockade of ERK1/2 nuclear accumulation. In response to AngII, PEA-15 overexpression displays the same functional consequences on ERK1/2 signaling as Akt overactivation. Thus, Akt overactivation prevents the nuclear translocation of ERK1/2 and the AngII-induced proliferation through interaction with and stabilization of endogenous PEA-15.