Activation and depalmitoylation of Gs alpha.
[3H]palmitate attached to mutationally activated alpha s (alpha s-R201C) turns over rapidly, compared with palmitate linked to normal alpha s (t1/2 approximately 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.
Wedegaertner
P B
PB
Department of Pharmacology, University of California, San Francisco 94143.
Bourne
H R
HR
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002451:Cell Compartmentation; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D010168:Palmitates / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction
D000318:Adrenergic beta-Agonists; D010168:Palmitates; D005576:Colforsin; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D007545:Isoproterenol