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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 Ser(29) in a serum-dependent manner. Replacement of Ser(29) to aspartic acid, which mimics the phosphorylation of Ser(29), 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.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Won M,Park KA,Byun HS,Kim YR,Choi BL,Hong JH,Park J,Seok JH,Lee YH,Cho CH,Song IS,Kim YK,Shen HM,Hur GM

doi

10.1016/j.jhep.2009.02.027

subject

Has Abstract

pub_date

2009-07-01 00:00:00

pages

67-76

issue

1

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(09)00225-6

journal_volume

51

pub_type

杂志文章

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