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Volume 271, Number 44, Issue of November 1, 1996 pp. 27585-27589
©1996 by The American Society for Biochemistry and Molecular Biology, Inc.

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Effect of Insulin on Farnesyltransferase Activity in 3T3-L1 Adipocytes

(Received for publication, March 28, 1996, and in revised form, August 8, 1996)

From the Medical Research Service and the Department of Medicine, Veterans Affairs Medical Center and the University of Colorado Health Sciences Center, Denver, Colorado 80220

Activation of p21^ras by GTP loading is a critical step in a cascade of intracellular insulin signaling. Farnesylation of p21^ras protein is an obligatory event that facilitates Ras migration to the plasma membrane and subsequent activation. Farnesyltransferase (FTase) is a ubiquitous enzyme that catalyzes the lipid modification of p21^ras by the addition of farnesyl to the C-terminal ``CAAX'' motif. In vitro and in vivo FTase activities were studied in 3T3-L1 adipocytes in response to insulin challenge. Insulin exerted a biphasic stimulatory effect on FTase activity measured in vitro with a 31% increase at 5 min and a 130% increase at 60 min. Insulin-stimulated farnesylation of p21^ras pools in vivo correlated with FTase activity seen in vitro by displaying an increase in farnesylated p21^ras from 40% of total cellular Ras in control cells to 63% by 5 min and 80% by 60 min (p < 0.05) in insulin-treated cells. Insulin challenge of 3T3-L1 adipocytes increased incorporation of tritiated mevalonic acid in p21^ras in a dose-dependent manner and stimulated a 2-fold increase in phosphorylation of the -subunit of FTase at 5 min and a 4-fold increase at 60 min.

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