Protein kinase SGK1 enhances MEK/ERK complex formation through the phosphorylation of ERK2: Implication for the positive regulatory role of SGK1 on the ERK function during liver regeneration

Abstract

Background/Aims: Based on the observation of biphasic induction of SGK1 expression in the regenerating liver, we investigated the role of SGK1 in the regulation of MEK/ERK signaling pathway which plays a crucial role in regulating growth and survival signaling. Methods: To determine the role of SGK1 in the activation of MEK/ERK signaling cascade, we infected primary hepatocytes with recombinant adenoviral vector encoding SGK1, and assessed its effect on the MEK/ERK signaling pathway. Results: Partial hepatectomy resulted in the biphasic transcriptional induction of SGK1 in regenerating liver tissues. Infection of primary hepatocytes with an adenoviral vector encoding SGK1 enhanced the ERK phosphorylation under serum-starved conditions and this was blocked by the expression of kinase-dead SGK1. SGK1 was found to physically interact with ERK1/2 as well as MEK1/2. Furthermore, SGK1 mediated the phosphorylation of ERK2 on Ser29 in a serum-dependent manner. Replacement of Ser29 to aspartic acid, which mimics the phosphorylation of Ser29, enhanced the ERK2 activity as well as the MEK/ERK complexes formation. Conclusions: SGK1 expression during liver regeneration is a part of a signaling pathway that is necessary for enhancing ERK signaling activation through modulating the MEK/ERK complex formation. © 2009 European Association for the Study of the Liver.