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Protein Kinase Dyrk1 Activates cAMP Response Element-binding Protein during Neuronal Differentiation in Hippocampal Progenitor Cells

Authors
 Eun Jin Yang  ;  Young Soo Ahn  ;  Kwang Chul Chung 
Citation
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.276(43) : 39819-39824, 2001 
Journal Title
 JOURNAL OF BIOLOGICAL CHEMISTRY 
ISSN
 0021-9258 
Issue Date
2001
MeSH
Animals ; Cell Differentiation ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Down Syndrome/etiology ; Fibroblast Growth Factor 2/pharmacology ; Gene Expression Regulation, Developmental ; Hippocampus/cytology* ; Humans ; Neurons/cytology* ; Phosphorylation ; Protein Binding ; Protein-Serine-Threonine Kinases/metabolism* ; Protein-Tyrosine Kinases/metabolism* ; Rats ; Stem Cells/cytology* ; Transcription, Genetic/drug effects ; Two-Hybrid System Techniques
Abstract
Dyrk is a dual specific protein kinase thought to be involved in normal embryo neurogenesis and brain development. Defects/imperfections in this kinase have been suggested to play an important role in the mental retardation of patients with Down's syndrome. The transcriptional factor cAMP response element-binding protein (CREB) has been implicated in the formation of many types of synaptic plasticity, such as learning and memory. In the present study we show that Dyrk1 activity is markedly induced during the differentiation of immortalized hippocampal progenitor (H19-7) cells. The addition of a neurogenic factor, basic fibroblast growth factor, to the H19-7 cells results in an increased specific binding of Dyrk1 to active CREB. In addition, Dyrk1 directly phosphorylates CREB, leading to the stimulation of subsequent CRE-mediated gene transcription during the neuronal differentiation in H19-7 cells. Blockade of Dyrk1 activation significantly inhibits the neurite outgrowth as well as CREB phosphorylation induced by basic fibroblast growth factor. These findings suggest that Dyrk1 activation and subsequent CREB phosphorylation is important in the neuronal differentiation of central nervous system hippocampal cells.
Files in This Item:
T200101931.pdf Download
DOI
10.1074/jbc.M104091200
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pharmacology (약리학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Young Soo(안영수)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/142276
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