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Proc Natl Acad Sci U S A. 1993 Feb 1;90(3):868-72.

Protein prenylcysteine analog inhibits agonist-receptor-mediated signal transduction in human platelets.

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Department of Biological Sciences, Ohio University, Athens 45701.


Signal transduction components, including the Ras superfamily of low molecular weight GTP-binding proteins and the gamma subunits of heterotrimeric G proteins, are reversibly carboxyl methylated at C-terminal prenylcysteine residues. We have previously shown that the prenylcysteine analog N-acetyl-S-trans,trans-farnesyl-L-cysteine (AFC) inhibits carboxyl methylation of these proteins in human platelets. Here we show that concentrations of AFC that inhibit Ras carboxyl methylation (10-50 microM) also block responses to agonists such as ADP, collagen, arachidonic acid, U46619 (a stable analog of prostaglandin H2), thrombin, and guanosine 5'-[gamma-thio]triphosphate. AFC does not inhibit aggregation induced by effectors such as ionomycin, phorbol 12,13-dibutyrate, and bacterial phospholipase C that bypass G proteins to activate platelets at the level of cytosolic Ca2+ concentration and protein kinase C. These findings indicate that AFC inhibits agonist-receptor-mediated signal transduction in human platelets.

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