Agonist stimulation increases the turnover rate of beta 2AR-bound palmitate and promotes receptor depalmitoylation

Biochemistry
T P LoiselMichel Bouvier

Abstract

We have characterized the dynamic nature of beta 2-adrenergic receptor palmitoylation in Sf9 cells. Under basal conditions, the turnover of receptor-bound palmitate is rapid (half-life = 9.8 +/- 1.8 min) compared to the turnover rate of the receptor protein itself (half-life = 109 +/- 10 min). This suggests that an equilibrium between the palmitoylated and nonpalmitoylated forms of the receptor exists at resting state. Stimulation of the receptor by the agonist isoproterenol reduces the half-life of the beta 2-adrenergic receptor-bound palmitate by 1.8 fold without affecting the turnover rate of the receptor itself. Upon sustained stimulation, this increased palmitate turnover rate shifted the equilibrium toward the nonpalmitoylated form of the receptor, suggesting that prolonged activation either increases the rate of depalmitoylation or prevents receptor palmitoylation. Consistent with the latter possibility, pretreatment of cells with agonist, prior to metabolic labeling, reduced the incorporation of [3H]palmitate into the beta 2-adrenergic receptor by more than 80%. This suggests a link between receptor desensitization occurring upon sustained agonist stimulation and the decrease in receptor palmitoylation. Supporting this ...Continue Reading

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