Members of the Ras superfamily of G proteins, γ-subunits of heterotrimeric G proteins and the α-subunit of cGMP phosphodiesterase from retinal rods are all carboxyl methylated at carboxy-terminal S-farnesylcysteine residues. AFC specifically inhibits the S-farnesylcysteine methyl transferase (Km=20 µM) in cell free extracts and in whole cells. It inhibits carboxyl methylation of p21ras platelet Rap15 and the γ-subunit of transducin. It blocks receptor-mediated signal transduction in platelets and neutrophils not by inhibiting the methyltransferase, but possibly by inhibiting capacitative Ca2+ entry.
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