LIPID MODIFICATIONS OF G-PROTEINS - ALPHA-SUBUNITS ARE PALMITOYLATED

A small number of membrane-associated proteins are reversibly and cova lently modified with palmitic acid. Palmitoylation of G-protein alpha and beta subunits was assessed by metabolic labeling of subunits expre ssed in simian COS cells or insect Sf9 cells. The fatty acid was incor porated into all of the alpha subunits examined (alpha(s), alpha(o), a lpha(i1), alpha(i2), alpha(i3), alpha(z), and alpha(q)), including tho se that are also myristoylated (alpha(o), alpha(i), and alpha(z)). Pal mitate was released by treatment with base, suggesting attachment to t he protein through a thioester or ester bond. Limited tryptic digestio n of activated alpha(o) and alpha(s) resulted in release of the amino- terminal portions of the proteins and radioactive palmitate. These dat a are consistent with palmitoylation of the proteins near their amino termini, most likely on Cys-3. Reversible acylation of G-protein alpha subunits may provide an additional mechanism for regulation of signal transduction.