title: Regulation of a third conserved phosphorylation site in SGK1.
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.
authors.affiliation: Department of Pharmacology and Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9041, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
authors.forename: Bing-e
authors.initials: BE
authors.lastname: Xu
authors.forename: Yu-Chi
authors.initials: YC
authors.lastname: Juang
authors.forename: Steve
authors.initials: S
authors.lastname: Stippec
authors.forename: Yingming
authors.initials: Y
authors.lastname: Zhao
authors.forename: Melanie H
authors.initials: MH
authors.lastname: Cobb
mesh_terms: D020816:Amino Acid Motifs / Q000502:physiology; D056827:Endosomal Sorting Complexes Required for Transport; D004789:Enzyme Activation / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D009154:Mutation; D000075702:Nedd4 Ubiquitin Protein Ligases; D010766:Phosphorylation / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism; D000076204:WNK Lysine-Deficient Protein Kinase 1; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D017874:Immediate-Early Proteins; D047908:Intracellular Signaling Peptides and Proteins; D015778:Minor Histocompatibility Antigens; D000075702:Nedd4 Ubiquitin Protein Ligases; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D044767:Ubiquitin-Protein Ligases; D000076204:WNK Lysine-Deficient Protein Kinase 1; D000099184:Serum-Glucocorticoid Regulated Kinases; C000618483:Nedd4 protein, human; C000618485:Nedd4L protein, human; C494918:AKT1 protein, human; C498743:WNK1 protein, human