Department of Biology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Korea.
Exp Neurobiol. 2011 Mar;20(1):35-44. doi: 10.5607/en.2011.20.1.35. Epub 2011 Mar 31.
Dual-specificity tyrosine (Y)-phosphorylation-regulated protein kinase 1A (Dyrk1A) is the mammalian homologue of Drosophila melanogaster minibrain and its human gene is mapped to the Down syndrome critical region of chromosome 21. Dyrk1A phosphorylates several transcription factors, including NFAT and CREB and a number of cytosolic proteins such as APP, tau, and α-synuclein. Although Dyrk1A is involved in the control of cell growth and postembryonic neurogenesis, its potential role during cell death and signaling pathway is not clearly understood. In the present study, we show that Dyrk1A is activated under the condition of apoptotic cell death. In addition, Dyrk1A is coupled to JNK1 activation, and directly interacts with apoptosis signal-regulating kinase 1 (ASK1). Moreover, Dyrk1A positively regulates ASK1-mediated JNK1-signaling, and appears to directly phosphorylate ASK1. These data indicate that Dyrk1A regulates cell death through facilitating ASK1-mediated signaling events.
双特异性酪氨酸（Y）磷酸化调节蛋白激酶 1A（Dyrk1A）是果蝇 melanogaster 小脑畸形的哺乳动物同源物，其人类基因定位于 21 号染色体唐氏综合征关键区域。Dyrk1A 磷酸化几种转录因子，包括 NFAT 和 CREB，以及一些细胞质蛋白，如 APP、tau 和 α-突触核蛋白。尽管 Dyrk1A 参与细胞生长和胚胎后神经发生的控制，但它在细胞死亡和信号通路中的潜在作用尚不清楚。在本研究中，我们表明 Dyrk1A 在凋亡细胞死亡的条件下被激活。此外，Dyrk1A 与 JNK1 的激活偶联，并直接与凋亡信号调节激酶 1（ASK1）相互作用。此外，Dyrk1A 正向调节 ASK1 介导的 JNK1 信号转导，并似乎直接磷酸化 ASK1。这些数据表明 Dyrk1A 通过促进 ASK1 介导的信号事件来调节细胞死亡。
