Normal activation of p70 S6 kinase by insulin in cells overexpressing dominant negative 85kD subunit of phosphoinositide 3-kinase
Hara, K.; Yonezawa, K.; Sakaue, H.; Kotani, K.; Kotani, K.; Kojima, A.; Waterfield, M.D.; Kasuga, M.
Biochemical and Biophysical Research Communications 208(2): 735-741
1995
ISSN/ISBN: 0006-291X PMID: 7695630 Document Number: 453109
The role of heteromeric phosphoinositide (PI) 3-kinase activity in insulin signal transduction was studied by investigating the effects of (i) overexpression of a dominant negative mutant p85 (DELTA-p85) that lacks the binding site for p110 (DELTA-p85-overexpressing cells) and (ii) inhibition of PI 3-kinase activity by wortmannin (wortmannin-treated cells). The insulin-induced association of PI 3-kinase activity with insulin receptor substrate-1(IRS-1) was inhibited in both wortmannin-treated cells and DELTA-p85-overexpressing cells. However, whereas insulin-induced activation of p70 S6 kinase was completely abolished in wortmannin-treated cells, it appeared normal in DELTA-p85-overexpressing cells. These results raise the possibility that a wortmannin-sensitive pathway independent of heteromeric PI 3-kinase is involved in the activation of p70 S6 kinase by insulin.