Negative regulation of SEK1 signaling by serum- and glucocorticoid- inducible protein kinase 1

Myung Jin Kim, Ji Soo Chae, Kwang Je Kim, Sang Gil Hwang, Kyoung Wan Yoon, Eun Kyung Kim, Hee Jae Yun, Jun Ho Cho, Jeehyun Kim, Bong Woo Kim, Hyung Chul Kim, Sang Sun Kang, Florian Lang, Ssang Goo Cho, Eui Ju Choi

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Serum- and glucocorticoid-inducible protein kinase 1 (SGK1) has been implicated in diverse cellular activities including the promotion of cell survival. The molecular mechanism of the role of SGK1 in protection against cellular stress has remained unclear, however. We have now shown that SGK1 inhibits the activation of SEK1 and thereby negatively regulates the JNK signaling pathway. SGK1 was found to physically associate with SEK1 in intact cells. Furthermore, activated SGK1 mediated the phosphorylation of SEK1 on serine 78, resulting in inhibition of the binding of SEK1 to JNK1, as well as to MEKK1. Replacement of serine 78 of SEK1 with alanine abolished SGK1-mediated SEK1 inhibition. Oxidative stress upregulated SGK1 expression, and depletion of SGK1 by RNA interference potentiated the activation of SEK1 induced by oxidative stress in Rat2 fibroblasts. Moreover, such SGK1 depletion prevented the dexamethasone-induced increase in SGK1 expression, as well as the inhibitory effects of dexamethasone on paclitaxel-induced SEK1-JNK signaling and apoptosis in MDA-MB-231 breast cancer cells. Together, our results suggest that SGK1 negatively regulates stress-activated signaling through inhibition of SEK1 function.

Original languageEnglish
Pages (from-to)3075-3085
Number of pages11
JournalEMBO Journal
Volume26
Issue number13
DOIs
Publication statusPublished - 2007 Jul 11

Keywords

  • Dexamethasone
  • Paclitaxel
  • SEK1/SGK1
  • c-Jun NH-terminal kinase

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Fingerprint Dive into the research topics of 'Negative regulation of SEK1 signaling by serum- and glucocorticoid- inducible protein kinase 1'. Together they form a unique fingerprint.

  • Cite this

    Kim, M. J., Chae, J. S., Kim, K. J., Hwang, S. G., Yoon, K. W., Kim, E. K., Yun, H. J., Cho, J. H., Kim, J., Kim, B. W., Kim, H. C., Kang, S. S., Lang, F., Cho, S. G., & Choi, E. J. (2007). Negative regulation of SEK1 signaling by serum- and glucocorticoid- inducible protein kinase 1. EMBO Journal, 26(13), 3075-3085. https://doi.org/10.1038/sj.emboj.7601755