Stimulation of mitogenesis by a cell-permeable PI 3-kinase binding peptide.
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.
Derossi
D
D
Department of Experimental Pathology, King's College London GKT Medical School, Guy's Hospital Campus, London, SE1 9RT, United Kingdom.
Williams
E J
EJ
Green
P J
PJ
Dunican
D J
DJ
Doherty
P
P
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002478:Cells, Cultured; D051379:Mice; D008938:Mitosis / Q000187:drug effects*; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism / Q000502:physiology*; D011930:Reaction Time; D018909:src Homology Domains / Q000187:drug effects
D002352:Carrier Proteins; D010455:Peptides; D019869:Phosphatidylinositol 3-Kinases