Stimulation of Mitogenesis by a Cell-Permeable PI 3-Kinase Binding Peptide

• Published in: Biochemical and biophysical research communications Vol. 251; no. 1; pp. 148 - 152
• Main Authors: Derossi, Daniele, Williams, Emma J., Green, Paula J., Dunican, Dara J., Doherty, Patrick
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.10.1998
• Subjects: 3T3 Cells; Amino Acid Sequence; Animals; Carrier Proteins - chemical synthesis; Carrier Proteins - metabolism; Carrier Proteins - pharmacology; Cell Membrane Permeability - drug effects; cell proliferation; cell-permeable peptides; Cells, Cultured; FGF; Mice; Mitosis - drug effects; Molecular Sequence Data; Peptides - chemical synthesis; Peptides - metabolism; Peptides - pharmacology; Phosphatidylinositol 3-Kinases - metabolism; Phosphatidylinositol 3-Kinases - physiology; PI 3-kinase; Reaction Time; src Homology Domains - drug effects; PI 3-kinase; cell proliferation; FGF; cell-permeable peptides
• ISSN: 0006-291X; 1090-2104
• 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 enzymein 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.