Adayev Tatyana, Chen-Hwang Mo-Chou, Murakami Noriko, Wang Rong, Hwang Yu-Wen
Molecular Biology Department, NYS Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA.
Biochem Biophys Res Commun. 2006 Dec 29;351(4):1060-5. doi: 10.1016/j.bbrc.2006.10.169. Epub 2006 Nov 7.
MNB/DYRK1A is a proline-directed serine/threonine kinase implicated in Down syndrome (DS). In an earlier screening, two proteins from adult rat brain, one 100kDa and the other 140 kDa, were found to be prominently phosphorylated by the kinase. The 100-kDa protein was previously characterized as an isoform of dynamin 1. In this study, we identified the 140-kDa protein as synaptojanin 1 (SJ1). MNB/DYRK1A phosphorylates SJ1 at multiple sites and produces complex behaviors in binding to amphiphysin 1 and intersectin 1 (ITSN1). However, the phosphorylation has little effect on the phosphatidylinositol phosphatase activity of SJ1. These results suggest that MNB/DYRK1A is involved in regulating the recruitment activity but not the phosphatase activity of SJ1. Our findings may be especially important in the etiology of DS because MNB/DYRK1A, SJ1, and ITSN1 are all located at or near the region of human chromosome 21, which is postulated to be involved in the disease.
MNB/DYRK1A是一种与唐氏综合征（DS）相关的脯氨酸定向丝氨酸/苏氨酸激酶。在早期筛查中，发现来自成年大鼠大脑的两种蛋白质，一种100kDa，另一种140kDa，被该激酶显著磷酸化。100kDa的蛋白质先前被鉴定为发动蛋白1的一种同工型。在本研究中，我们将140kDa的蛋白质鉴定为突触素1（SJ1）。MNB/DYRK1A在多个位点磷酸化SJ1，并在与发动蛋白1和相交蛋白1（ITSN1）结合时产生复杂行为。然而，磷酸化对SJ1的磷脂酰肌醇磷酸酶活性影响很小。这些结果表明，MNB/DYRK1A参与调节SJ1的募集活性而非磷酸酶活性。我们的发现可能在DS的病因学中尤为重要，因为MNB/DYRK1A、SJ1和ITSN1都位于人类21号染色体区域或其附近，据推测该区域与该疾病有关。
