Contribution of endogenous G-protein-coupled receptor kinases to Ser129 phosphorylation of α-synuclein in HEK293 cells
Contribution of endogenous G-protein-coupled receptor kinases to Ser129 phosphorylation of α-synuclein in HEK293 cells
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DOI：
10.1016/j.bbrc.2009.04.130
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发表时间：
2009-07-03
影响因子：
3.1
通讯作者：
Kato, Takeo
中科院分区：
文献类型：
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作者：
Sakamoto, Masahiro;Arawaka, Shigeki;Kato, Takeo
沉积在路易体中的大部分α-突触核蛋白（α S）（帕金森病（PD）的病理标志）在丝氨酸129（Ser 129）处磷酸化。已证明α S的Ser 129磷酸化增强了果蝇PD模型中α S对多巴胺能神经元的毒性。在Set 129处的α S磷酸化似乎在PD的发病机制中起关键作用。在此，我们评估了G蛋白偶联受体激酶家族（GRK 2、GRK 3、GRK 5和GRK 6）的普遍表达成员对HEK 293细胞中α S的Ser 129磷酸化的贡献。为了选择性地降低细胞中GRK家族每个成员的内源性表达，我们使用了小干扰RNA。GRK 3或GRK 6的敲低显著降低了α S的Ser 129磷酸化：然而，GRK 2或GRK 5的敲低并不降低α S磷酸化。结果表明，内源性GRK 3和GRK 6而不是GRK 2或GRK 5有助于HEK 293细胞中α S的Ser 129磷酸化。(C)2009爱思唯尔公司All rights reserved.
The majority of alpha-synuclein (alpha S) deposited in Lewy bodies, the pathological hallmark of Parkinson's disease (PD), is phosphorylated at serine 129 (Ser 129). Ser 129 phosphorylation of alpha S has been demonstrated to enhance the alpha S toxicity to dopaminergic neurons in a Drosophila model of PD. Phosphorylation of alpha S at Set 129 seems to play a crucial role in the pathogenesis of PD. Here, we assessed the contribution of ubiquitously expressing members of the G-protein-coupled receptor kinase family (GRK2, GRK3, GRK5, and GRK6) to Ser 129 phosphorylation of alpha S in HEK293 cells. To selectively reduce the endogenous expression of each member of the GRK family in cells, we used small interfering RNAs. Knockdown of GRK3 or GRK6 significantly decreased Ser129 phosphorylation of alpha S: however, knockdown of GRK2 or GRK5 did not decrease alpha S phosphorylation. The results indicate that endogenous GRK3 and GRK6 but not GRK2 or GRK5, contribute to Ser129 phosphorylation of alpha S in HEK293 cells. (C) 2009 Elsevier Inc. All rights reserved.