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

被引:64
作者
Derossi, D [1 ]
Williams, EJ [1 ]
Green, PJ [1 ]
Dunican, DJ [1 ]
Doherty, P [1 ]
机构
[1] Kings Coll London, GKT Med Sch, Dept Expt Pathol, London SE1 9RT, England
关键词
PI; 3-kinase; cell-permeable peptides; cell proliferation; FGF;
D O I
10.1006/bbrc.1998.9444
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 60 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 60 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. (C) 1998 Academic Press.
引用
收藏
页码:148 / 152
页数:5
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