PROBING CELLULAR FUNCTIONS OF THE MINIBRAIN KINASE

探索小脑激酶的细胞功能

• 批准号: 6027955
• 负责人: YU-WEN HWANG
• 金额: $ 21.47万
• 依托单位: INSTITUTE FOR BASIC RES IN DEV DISABIL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-03-01 至 2005-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6027955
• 关键词: Downs syndrome; PC12 cells; dynamin; endocytosis; enzyme activity; phosphoproteins; protein kinase; tissue /cell culture; yeast two hybrid system

The Minibrain (Mnb) gene is mapped to the Down syndrome critical region of human chromosome 21. Evidence suggests that an elevated Mnb gene dosage, as in trisomy 21, contributes to Down syndrome phenotypes. The Mnb encodes a dual specificity protein kinase whose cellular function has yet to be determined. Our preliminary results suggest that MnB kinase is involved in controlling the activity of dynamin-1, while its enzymatic activity is in turn regulated by rabaptin-5 and a novel cysteine-rich protein. Since both dynamin-1 and rabaptin-5 are part of endocytosis machinery, it also suggests that the Mnb kinase must play an essential role in regulating endocytic membrane trafficking. We plan to pursue the following specific aims in this study: 1. To establish the Mnb kinase as the enzyme responsible for regulating dynamin-1 physiological activity through phosphorylation. 2. To determine the mechanisms of regulating the enzymatic activity of Mnb kinase by rabaptin-5 and the cysteine-rich protein. 3. To characterize the biochemical properties of dynamin-12 phosphorylated by Mnb kinase. 4. To study the effects of Mnb kinase over-expression on endocytic membrane trafficking.

Minibrain（Mnb）基因定位于人类21号染色体的唐氏综合征关键区域。有证据表明，Mnb基因剂量升高，如21三体，有助于唐氏综合征表型。Mnb编码一种双特异性蛋白激酶，其细胞功能尚未确定。我们的初步研究结果表明，MnB激酶参与控制发动蛋白-1的活性，而其酶活性反过来又受到Rabaptin-5和一种新的富含半胱氨酸的蛋白质的调节。由于发动蛋白-1和Rabaptin-5都是内吞机制的一部分，因此也表明Mnb激酶必须在调节内吞膜运输中发挥重要作用。我们计划在这项研究中实现以下具体目标：1。建立Mnb激酶作为负责通过磷酸化调节发动蛋白-1生理活性的酶。2.探讨Rabaptin-5和富含半胱氨酸蛋白对Mnb激酶活性的调节机制。3.目的研究Mnb激酶磷酸化dynamin-12的生物化学特性。4.研究Mnb激酶过表达对细胞内吞膜转运的影响。