Dephosphorylation of clustered phosphoserine residues in human Grb14 by protein phosphatase 1 and its effect on insulin receptor complex formation

J Pept Sci. 2019 Oct;25(10):e3207. doi: 10.1002/psc.3207. Epub 2019 Jul 25.


The physical interaction of the human growth factor receptor-bound protein 14 (hGrb14) and the insulin receptor (IR) represses insulin signaling. With respect to the recruiting mechanism of hGrb14 to IR respond to insulin stimulus, our previous reports have suggested that phosphorylation of Ser358 , Ser362 , and Ser366 in hGrb14 by glycogen synthase kinase-3 repressed hGrb14-IR complex formation. In this study, we investigated phosphatase-mediated dephosphorylation of the hGrb14 phosphoserine residues. An in vitro phosphatase assay with hGrb14-derived synthetic phosphopeptides suggested that protein phosphatase 1 (PP1) is involved in the dephosphorylation of Ser358 and Ser362 . Furthermore, coimmunoprecipitation experiments suggested that insulin-induced hGrb14-IR complex formation was repressed by the substitution of Ser358 or Ser362 with glutamic acid. These findings suggested that phosphate groups on Ser358 and Ser362 in hGrb14 are dephosphorylated by PP1, and the dephosphorylation facilitates hGrb14-IR complex formation.

Keywords: Grb14; insulin receptor; okadaic acid; protein phosphatase 1.

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • COS Cells
  • Chlorocebus aethiops
  • Hep G2 Cells
  • Humans
  • Phosphoserine / metabolism
  • Protein Phosphatase 1 / genetics
  • Protein Phosphatase 1 / metabolism*
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism*


  • Adaptor Proteins, Signal Transducing
  • GRB14 protein, human
  • Phosphoserine
  • Receptor, Insulin
  • Protein Phosphatase 1