Lipid modifications of G proteins: α subunits are palmitoylated

A small number of membrane-associated proteins are reversibly and covalently modified with palmitic acid. Palmitoylation of G-protein α and β subunits was assessed by metabolic labeling of subunits expressed in simian COS cells or insect Sf9 cells. The fatty acid was incorporated into all of the α subunits examined (α_s, α_o, α_i1, α_i2, α_i3, α_z, and α_q), including those that are also myristoylated (α_o, α_i, and α_z). Palmitate was released by treatment with base, suggesting attachment to the protein through a thioester or ester bond. Limited tryptic digestion of activated α_o and α_s resulted in release of the ammo-terminal portions of the proteins and radioactive palmitate. These data are consistent with palmitoylation of the proteins near their amino termini, most likely on Cys-3. Reversible acylation of G-protein α subunits may provide an additional mechanism for regulation of signal transduction.