My. Degtyarev et al., PALMITOYLATION OF A G-PROTEIN ALPHA(I) SUBUNIT REQUIRES MEMBRANE LOCALIZATION NOT MYRISTOYLATION, The Journal of biological chemistry, 269(49), 1994, pp. 30898-30903
Palmitoylation is a dynamic, post-translational modification of the am
ino terminus of heterotrimeric G protein alpha subunits. Since myristo
ylation, beta gamma interactions, and membrane attachment also involve
the amino terminus of the G protein alpha(i1) subunit, we studied the
relationships between palmitoylation and these events. Using COS cell
transfection, the turnover of palmitate was slower on alpha(i1) subun
its co-expressed with beta and gamma subunits than on the alpha(i1) su
bunit expressed alone. Mutation of cysteine 3 of alpha(i1) prevented [
H-3]palmitate but not [H-3]myristate incorporation and decreased the m
embrane localization of this protein. This nonpalmitoylated mutant cou
ld form a heterotrimer with co-expressed beta gamma subunits which res
tored its membrane localization. A nonmyristoylated alpha(i1) mutant (
glycine 2 to alanine) could incorporate [H-3]palmitate when co-express
ed with beta gamma subunits and localized to the membrane. The [H-3]pa
lmitate turnover of this nonmyristoylated mutant was more rapid than s
een with the wild-type alpha(i1) subunit. While myristoylation is not
required for palmitoylation, both myristoylation and beta gamma associ
ation can slow the turnover of palmitate on alpha(i1). These results s
uggest that palmitoylation maintains the membrane attachment of the fr
ee alpha subunit and changes in beta gamma association could modulate
palmitoylation during signaling.