ID OF MINIBRAIN KINASE/DUAL-SPECIFICITY YAK 1-RELATED KINASE 1A P-SITES IN DYN-

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。迷你脑激酶(Mnbk)/双特异性牦牛1相关激酶（Dyrk1A）基因位于人类21号染色体q21.22区，与唐氏综合征智力低下有关。Mnbk/Dyrk1A是一种脯氨酸导向的丝氨酸/苏氨酸激酶，它优先磷酸化序列RPX(S/T)P。此前，Mnbk/Dyrk1A被发现磷酸化动力蛋白1，并改变其与含SH3结构域蛋白的相互作用（Chen-Hwang, m.c. et al. J. Biol）。化学。277:17597-17604,2002)。在这项研究中，我们试图确定Mnbk/Dyrk1A在dynamin 1中的磷酸化位点。通过结合dynamin 1缺失突变体和合成肽，确定了三个潜在的Mnbk/Dyrk1A磷酸化位点Ser-778、-795和-857。随后通过质谱分析证实了Mnbk/ dyrk1a磷酸化的完整动力蛋白1 Ser-795和-857位点的磷酸化。一份手稿已提交出版。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The minibrain kinase (Mnbk)/dual specificity Yak 1 related kinase (Dyrk1A) gene is localized in the q21.22 region of human chromosome 21 and it has been associated with the mental retardation of Down syndrome. Mnbk/Dyrk1A is a proline-directed Ser/Thr kinase which preferentially phosphorylates the sequence RPX(S/T)P. Previously, Mnbk/Dyrk1A was found to phosphorylate dynamin 1 and alter its interactions with SH3 domain-containing proteins (Chen-Hwang, M. C. et. al. J. Biol. Chem. 277: 17597-17604, 2002). In this study, we sought to determine the Mnbk/Dyrk1A phosphorylation sites in dynamin 1. By a combination of dynamin 1 deletion mutants and synthetic peptides, three potential Mnbk/Dyrk1A phosphorylation sites, Ser-778, -795 and -857, were identified. Phosphorylation at Ser-795 and -857 was subsequently confirmed in Mnbk/Dyrk1A-phosphorylated intact dynamin 1 by mass spectroscopy. A manuscript has been submitted for publication.