National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing 100101, China.
FEBS Lett. 2010 Nov 19;584(22):4570-4. doi: 10.1016/j.febslet.2010.10.052. Epub 2010 Oct 28.
Regulator of G-protein signaling 4 (RGS4), an intracellular modulator of G-protein coupled receptor (GPCR)-mediated signaling, is regulated by multiple processes including palmitoylation and proteasome degradation. We found that co-expression of DHHC acyltransferases (DHHC3 or DHHC7), but not their acyltransferase-inactive mutants, increased expression levels of RGS4 but not its Cys2 to Ser mutant (RGS4C2S). DHHC3 interacts with and palmitoylates RGS4 but not RGS4C2S in vivo. Palmitoylation prolongs the half-life of RGS4 by over 8-fold and palmitoylated RGS4 blocked α(1A)-adrenergic receptor-stimulated intracellular Ca(2+) mobilization. Together, our findings revealed that DHHC proteins could regulate GPCR-mediated signaling by increasing RGS4 stability.
G 蛋白信号调节因子 4（RGS4）是 G 蛋白偶联受体（GPCR）介导信号的细胞内调节剂，其表达受到多种调控机制的影响，包括棕榈酰化和蛋白酶体降解。我们发现，DHHC 酰基转移酶（DHHC3 或 DHHC7）的共表达，而不是其酰基转移酶失活突变体的共表达，会增加 RGS4 的表达水平，但不会增加其半胱氨酸 2 到丝氨酸突变体（RGS4C2S）的表达水平。DHHC3 与 RGS4 相互作用并对其进行棕榈酰化，而不会对 RGS4C2S 进行棕榈酰化。棕榈酰化使 RGS4 的半衰期延长了 8 倍以上，并且棕榈酰化的 RGS4 阻断了 α(1A)-肾上腺素能受体刺激的细胞内 Ca(2+)动员。综上所述，我们的研究结果表明，DHHC 蛋白可以通过增加 RGS4 的稳定性来调节 GPCR 介导的信号转导。
