کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6278008 | 1295785 | 2008 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The down syndrome candidate dual-specificity tyrosine phosphorylation-regulated kinase 1A phosphorylates the neurodegeneration-related septin 4
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
HSAPBRGSTDOXMNBpolybasic regionNFTPRDDYRK1AAlzheimer disease - بیماری آلزایمرParkinson disease - بیماری پارکینسونTrisomy 21 - تریستومی 21Protein interaction - تعامل پروتئینHarmine - حرمتNeurofibrillary tangle - خلط نوروفیبریلاScaffold - داربَستProline-rich domain - دامنه غنی پرولینdoxycycline - داکسی سایکلینdigoxigenin - دیگوکسین ژنDown syndrome - سندرم داونDIG - شماCoiled-coil - کویل کویلglutathione S-transferase - گلوتاتیون S-ترانسفراز
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The dual-specific kinase DYRK1A (dual-specificity tyrosine phosphorylation-regulated kinase 1A) is the mammalian orthologue of the Drosophila minibrain (MNB) protein kinase and executes diverse roles in neuronal development and adult brain physiology. DYRK1A is overexpressed in Down syndrome (DS) and has recently been implicated in several neurodegenerative diseases. In an attempt to elucidate the molecular basis of its involvement in cognitive and neurodegeneration processes, we searched for novel proteins interacting with the kinase domain of DYRK1A in the adult mouse brain and identified septin 4 (SEPT4, also known as Pnutl2/CDCrel-2). SEPT4 is a member of the group III septin family of guanosine triphosphate hydrolases (GTPases), which has previously been found in neurofibrillary tangles of Alzheimer disease brains and in α-synuclein-positive cytoplasmic inclusions in Parkinson disease brains. In transfected mammalian cells, DYRK1A specifically interacts with and phosphorylates SEPT4. Phosphorylation of SEPT4 by DYRK1A was inhibited by harmine, which has recently been identified as the most specific inhibitor of DYRK1A. In support of a physiological relation in the brain, we found that Dyrk1A and Sept4 are co-expressed and co-localized in neocortical neurons. These findings suggest that SEPT4 is a substrate of DYRK1A kinase and thus provide a possible link for the involvement of DYRK1A in neurodegenerative processes and in DS neuropathologies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 157, Issue 3, 2 December 2008, Pages 596-605
Journal: Neuroscience - Volume 157, Issue 3, 2 December 2008, Pages 596-605
نویسندگان
J.H. Sitz, K. Baumgärtel, B. Hämmerle, C. Papadopoulos, P. Hekerman, F.J. Tejedor, W. Becker, B. Lutz,