Regulation of a third conserved phosphorylation site in SGK1

Wei Chen, Yue Chen, Bing E. Xu, Yu Chi Juang, Steve Stippec, Yingming Zhao, Melanie H. Cobb

15 Scopus citations

Abstract

SGK1 (serum- and glucocorticoid-induced kinase 1) is a member of the AGC branch of the protein kinase family. Among well described functions of SGK1 is the regulation of epithelial transport through phosphorylation of the ubiquitin protein ligase Nedd4-2 (neuronal precursor cell expressed developmentally down-regulated 4-2). The activation of SGK1 has been widely accepted to be dependent on the phosphorylation of Thr256 in the activation loop and Ser422 in the hydrophobic motif near the C terminus. Here, we report the identification of two additional phosphorylation sites, Ser397 and Ser401. Both are required for maximum SGK1 activity induced by extracellular agents or by coexpression with other protein kinases, with the largest loss of activity from mutation of Ser397. Coexpression with active Akt1 increased the phosphorylation of Ser397 and thereby SGK1 kinase activity. SGK1 activation was further augmented by coexpression with the protein kinase WNK1(with no lysine kinase 1). These findings reveal further complexity underlying the regulation of SGK1 activity.

Original languageEnglish (US)
Pages (from-to)3453-3460
Number of pages8
JournalJournal of Biological Chemistry
Volume284
Issue number6
DOIs
StatePublished - Feb 6 2009

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Regulation of a third conserved phosphorylation site in SGK1. / Chen, Wei; Chen, Yue; Xu, Bing E.; Juang, Yu Chi; Stippec, Steve; Zhao, Yingming; Cobb, Melanie H.

In: Journal of Biological Chemistry, Vol. 284, No. 6, 06.02.2009, p. 3453-3460.

Research output: Contribution to journalArticle