Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Androstadienes / pharmacology
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Animals
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CHO Cells
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Cricetinae
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Enzyme Activation / drug effects
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In Vitro Techniques
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Insulin / pharmacology*
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Insulin Receptor Substrate Proteins
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Molecular Sequence Data
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Phosphatidylinositol 3-Kinases
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Phosphoproteins / metabolism
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Phosphotransferases (Alcohol Group Acceptor) / antagonists & inhibitors
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Protein Serine-Threonine Kinases / metabolism*
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Rats
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Receptor, Insulin / metabolism*
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Recombinant Proteins
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Ribosomal Protein S6 Kinases
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Signal Transduction
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Wortmannin
Substances
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Androstadienes
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Insulin
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Insulin Receptor Substrate Proteins
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Irs1 protein, rat
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Phosphoproteins
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Recombinant Proteins
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Phosphotransferases (Alcohol Group Acceptor)
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Receptor, Insulin
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Protein Serine-Threonine Kinases
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Ribosomal Protein S6 Kinases
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Wortmannin