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J Biol Chem, Vol. 273, Issue 37, 23892-23896, September 11, 1998

Effect of Insulin on Farnesyltransferase
SPECIFICITY OF INSULIN ACTION AND POTENTIATION OF NUCLEAR EFFECTS OF INSULIN-LIKE GROWTH FACTOR-1, EPIDERMAL GROWTH FACTOR, AND PLATELET-DERIVED GROWTH FACTOR

Marc L. Goalstone, J. Wayne Leitner, Kei Wall, Lior Dolgonos, Kristina I. Rother, Domenico Accili, and Boris Draznin

From the Research Service and the Department of Medicine, Denver Veterans Affairs Medical Center and University of Colorado Health Sciences Center, Denver, Colorado 80220 and the  Developmental Endocrinology Branch, NICHD, National Institutes of Health, Bethesda, Maryland 20892

We have previously demonstrated that insulin activates farnesyltransferase (FTase) and augments the amounts of farnesylated p21 (Goalstone, M. L., and Draznin, B. (1996) J. Biol. Chem. 271, 27585-27589). We postulated that this aspect of insulin action might explain the "priming effect" of insulin on the cellular response to other growth factors. In the present study, we show the specificity of the effect of insulin on FTase. Insulin, but not insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), or platelet-derived growth factor (PDGF), stimulated the phosphorylation of the -subunit of FTase and the amounts of farnesylated p21. Even though all four growth factors utilized the Ras pathway to stimulate DNA synthesis, only insulin used this pathway to influence FTase. Insulin failed to stimulate FTase in cells expressing the chimeric insulin/IGF-1 receptor and in cells derived from the insulin receptor knock-out animals. Insulin potentiated the effects of IGF-1, EGF, and PDGF on DNA synthesis in cells expressing the wild type insulin receptor, but this potentiation was inhibited in the presence of the FTase inhibitor, -hydroxyfarnesylphosphonic acid. We conclude that the effect of insulin on FTase is specific, requires the presence of an intact insulin receptor, and serves as a conduit for the "priming" influence of insulin on the nuclear effects of other growth factors.

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Copyright © 1998 by The American Society for Biochemistry and Molecular Biology, Inc.

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