Abstract
Incubation of 3T3-L1 fibroblasts with insulin (10 nM or 100 nM) for 24 or 48 hours resulted in a significant increase in the amount of farnesylated p21Ras with a concomitant increase in the amount of GTP-loaded p21Ras. Cells preincubated with 100 nM insulin for 24 or 48 hours exhibited further 5-8 fold increases in p21Ras.GTP loading in response to an acute (10 minute) challenge with either insulin, EGF, or IGF-1. Effects of hyperinsulinemia were completely abolished by the presence of 1 microM alpha-hydroxyfarnesylphosphonic acid, a potent inhibitor of farnesyltransferase. These novel observations indicate that hyperinsulinemia increases the cellular pool of farnesylated p21Ras and thereby potentiates activation of p21Ras by growth factors.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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3T3 Cells
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Alkyl and Aryl Transferases*
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Animals
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Drug Synergism
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Enzyme Inhibitors / pharmacology
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Epidermal Growth Factor / pharmacology
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Farnesol / analogs & derivatives
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Farnesol / pharmacology
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Farnesyltranstransferase
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Growth Substances / pharmacology*
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Guanosine Triphosphate / metabolism
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Insulin / pharmacology*
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Insulin-Like Growth Factor I / pharmacology
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Mice
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Organophosphonates*
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Organophosphorus Compounds / pharmacology
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Protein Prenylation
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Proto-Oncogene Proteins p21(ras) / metabolism*
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Transferases / antagonists & inhibitors
Substances
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(alpha-hydroxyfarnesyl)phosphonic acid
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Enzyme Inhibitors
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Growth Substances
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Insulin
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Organophosphonates
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Organophosphorus Compounds
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Farnesol
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Epidermal Growth Factor
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Insulin-Like Growth Factor I
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Guanosine Triphosphate
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Transferases
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Alkyl and Aryl Transferases
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Farnesyltranstransferase
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Proto-Oncogene Proteins p21(ras)