Stimulation of mitogenesis by a cell-permeable PI 3-kinase binding peptide

Biochem Biophys Res Commun. 1998 Oct 9;251(1):148-52. doi: 10.1006/bbrc.1998.9444.


The binding of small phosphopeptides to the SH2 domains of the p85 regulatory subunit of PI 3-kinase can activate the enzyme in vitro. In the present study a cell-permeable peptide that binds specifically to the SH2 domains of p85 has been evaluated for its ability to stimulate a mitogenic response in the C2 muscle cell line. This peptide, in contrast to four other SH2-binding peptides, was as effective as serum, EGF, and FGF at stimulating entry into S-phase. The response to the p85 binding peptide, but not FGF, was inhibited by wortmannin and rapamycin, indicating that the peptide activates the PI 3-kinase/S6 kinase signalling pathway. The peptide response was not inhibited by the MEK inhibitor (PD098059) and did not stimulate Erk phosphorylation. Thus, there would appear to be no direct cross-talk between the pathway activated by the p85 binding peptide and the p42/p44 MAPK cascade.

MeSH terms

  • 3T3 Cells
  • Amino Acid Sequence
  • Animals
  • Carrier Proteins / chemical synthesis
  • Carrier Proteins / metabolism
  • Carrier Proteins / pharmacology*
  • Cell Membrane Permeability / drug effects*
  • Cells, Cultured
  • Mice
  • Mitosis / drug effects*
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / metabolism
  • Peptides / pharmacology*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphatidylinositol 3-Kinases / physiology*
  • Reaction Time
  • src Homology Domains / drug effects


  • Carrier Proteins
  • Peptides
  • Phosphatidylinositol 3-Kinases