Identification of different specificity requirements between SGK1 and PKBalpha

FEBS Lett. 2005 Feb 14;579(5):991-4. doi: 10.1016/j.febslet.2004.12.069. Epub 2005 Jan 13.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Immediate-Early Proteins
  • Molecular Sequence Data
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Peptides / chemistry
  • Peptides / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-akt
  • Spodoptera
  • Substrate Specificity

Substances

  • Immediate-Early Proteins
  • Nuclear Proteins
  • Peptides
  • Proto-Oncogene Proteins
  • Protein-Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • serum-glucocorticoid regulated kinase