Ishii Aasami, Nonaka Takashi, Taniguchi Sayuri, Saito Taro, Arai Tetsuaki, Mann David, Iwatsubo Takeshi, Hisanaga Shin-Ichi, Goedert Michel, Hasegawa Masato
Department of Molecular Neurobiology, Tokyo Institute of Psychiatry, 2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan.
FEBS Lett. 2007 Oct 2;581(24):4711-7. doi: 10.1016/j.febslet.2007.08.067. Epub 2007 Sep 6.
In Lewy body diseases and multiple system atrophy, alpha-synuclein is hyperphosphorylated at Ser129, suggesting a role in pathogenesis. Here, we report purification of the protein kinase in rat brain that phosphorylates Ser129 and its identification as casein kinase-2 (CK2). We show that most of the activity can be inhibited by heparin, an inhibitor of CK2. Phosphorylated Ser129 was detected in primary cultured neurons and inhibited by CK2 inhibitors. In some cases of Lewy body disease, CK2-like immunoreactivity was recovered in the sarkosyl-insoluble fraction, which was enriched in phosphorylated alpha-synuclein. Taken together, these findings suggest that CK2 may be involved in the hyperphosphorylation of alpha-synuclein in alpha-synucleinopathies.
在路易体病和多系统萎缩中，α-突触核蛋白在丝氨酸129位点发生过度磷酸化，提示其在发病机制中起作用。在此，我们报告了大鼠脑中使丝氨酸129磷酸化的蛋白激酶的纯化，并鉴定其为酪蛋白激酶2（CK2）。我们发现大部分活性可被CK2抑制剂肝素抑制。在原代培养的神经元中检测到磷酸化的丝氨酸129，且其被CK2抑制剂所抑制。在某些路易体病病例中，在富含磷酸化α-突触核蛋白的 Sarkosyl不溶性组分中恢复了CK2样免疫反应性。综上所述，这些发现表明CK2可能参与了α-突触核蛋白病中α-突触核蛋白的过度磷酸化。
