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

• Published in: Journal of hepatology Vol. 51; no. 1; pp. 67 - 76
• Main Authors: Won, Minho, Park, Kyeong Ah, Byun, Hee Sun, Kim, Young-Rae, Choi, Byung Lyul, Hong, Jang Hee, Park, Jongsun, Seok, Jeong Ho, Lee, Young-Ho, Cho, Chung-Hyun, Song, In Sang, Kim, Yong Kyung, Shen, Han-Ming, Hur, Gang Min
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.07.2009; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell signaling; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases - physiology; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immediate-Early Proteins - physiology; Liver regeneration; Liver Regeneration - physiology; MAP kinase; MAP Kinase Kinase 1 - physiology; MAP Kinase Kinase 2 - physiology; MAP Kinase Signaling System; Medical sciences; Mitogen-Activated Protein Kinase Kinases - physiology; NF-kappa B - metabolism; NF-κB; Phosphorylation; Protein-Serine-Threonine Kinases - physiology; Rats; Rats, Sprague-Dawley; SGK1; partial hepatectomy; serum and glucocorticoid-inducible protein kinase1; extracellular signal-regulated kinase; PKB; GST; MAP kinase; Cell signaling; NF-κB; MEK; glutathione S-transferase; PH; mitogen-activated protein kinase kinase; SGK1; Liver regeneration; protein kinase B; ERK; Phosphorylation; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Gastroenterology; Mitogen-activated protein kinase; Transcription factor NFκB
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2009.02.027

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.