Normal activation of p70 S6 kinase by insulin in cells overexpressing dominant negative 85kD subunit of phosphoinositide 3-kinase.
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 sustrate-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.
Hara
K
K
Second Department of Internal Medicine, Kobe University School of Medicine, Japan.
Yonezawa
K
K
Sakaue
H
H
Kotani
K
K
Kotani
K
K
Kojima
A
A
Waterfield
M D
MD
Kasuga
M
M
D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D008969:Molecular Sequence Data; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D011994:Recombinant Proteins; D019893:Ribosomal Protein S6 Kinases; D015398:Signal Transduction; D000077191:Wortmannin
D000730:Androstadienes; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin; D011994:Recombinant Proteins; D019893:Ribosomal Protein S6 Kinases; D000077191:Wortmannin; C526296:Irs1 protein, rat