ACTIVATION AND DEPALMITOYLATION OF G(S-ALPHA)

[H-3]palmitate attached to mutationally activated alpha(s) (alpha(s)-R201C) turns over rapidly, compared with palmitate linked to normal alpha(s) (t(1/2) approximate to 2 min versus 90 min); although alpha(s)-R201C (unlike normal alpha(s)) is predominantly found in the cytosol, [3H]palmitate is linked only to the membrane-bound pool of alpha(s), normal or mutant. Similarly, activation of wild-type alpha(s) by isoproterenol, a beta-adrenoceptor agonist that also induces membrane-to-cytosol translocation of alpha(s), dramatically accelerates depalmitoylation of alpha(s). Thus, activation-induced removal of palmitate provides an explanation for activation-induced shifts of alpha(s) to the cytosol. Regulated palmitoylation cycles provide a potential general mechanism for controlling reversible changes in the cellular location and activity of a protein.