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.

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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

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.

J Hepatol. 2009 Jul;51(1):67-76. doi: 10.1016/j.jhep.2009.02.027. Epub 2009 Apr 16.

PubMed ID
19447520 [ View in PubMed
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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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Dual specificity mitogen-activated protein kinase kinase 1Q02750Details
Mitogen-activated protein kinase 1P28482Details
Mitogen-activated protein kinase 3P27361Details
Serine/threonine-protein kinase Sgk1O00141Details
Dual specificity mitogen-activated protein kinase kinase 2P36507Details