title: Identification of different specificity requirements between SGK1 and PKBalpha.
abstract: NDRG1 is phosphorylated by SGK1 (but not PKB) in vivo at three residues each contained within three nonapeptide repeats. Here, we demonstrate that this nonapeptide, like the NDRG1 protein, is phosphorylated by SGK1, but not by PKBalpha or RSK1 in vitro. The inability of PKBalpha and RSK1 to phosphorylate the nonapeptide was traced to residues n+1, n+2 and n-4 (where n is the phosphorylation site). Changing them from Ser, Glu and Ser to Phe, Ala and Pro, respectively, transformed the nonapeptide into an excellent substrate for PKBalpha and RSK1. Our results identify a specific substrate for SGK1 and may facilitate detection of additional physiological substrates for this enzyme.
authors.affiliation: MRC Protein Phosphorylation Unit, School of Life Sciences, University of Dundee, Dundee DD1 5EH, Scotland, UK. j.t.c.murray@dundee.ac.uk
authors.forename: James T
authors.initials: JT
authors.lastname: Murray
authors.forename: Lorna A
authors.initials: LA
authors.lastname: Cummings
authors.forename: Graham B
authors.initials: GB
authors.lastname: Bloomberg
authors.forename: Philip
authors.initials: P
authors.lastname: Cohen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D017874:Immediate-Early Proteins; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D018411:Spodoptera; D013379:Substrate Specificity; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D010455:Peptides; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000099184:Serum-Glucocorticoid Regulated Kinases