FEBS Letters | |
Glucose induced MAPK signalling influences NeuroD1‐mediated activation and nuclear localization | |
Serup, Palle1  Stein, Roland2  Jensen, Jan N1  Petersen, Helle V1  | |
[1] Hagedorn Research Institute, Niels Steensensvej 6, DK-2820 Gentofte, Denmark;Vanderbilt Medical Center, Department of Molecular Physiology and Biophysics, 723 Light Hall, Nashville, TN 37232, USA | |
关键词: Insulin gene; Transcription; Phosphorylation; Regulation; | |
DOI : 10.1016/S0014-5793(02)03318-5 | |
学科分类:生物化学/生物物理 | |
来源: John Wiley & Sons Ltd. | |
【 摘 要 】
The helix–loop–helix transcription factor NeuroD1 (also known as Beta2) is involved in β-cell survival during development and insulin gene transcription in adults. Here we show NeuroD1 is primarily cytoplasmic at non-stimulating glucose concentrations (i.e. 3 mM) in MIN6 β-cells and nuclear under stimulating conditions (i.e. 20 mM). Quantification revealed that NeuroD1 was in 40–45% of the nuclei at 3 mM and 80–90% at 20 mM. Treatment with the MEK inhibitor PD98059 or substitution of a serine for an alanine at a potential mitogen-activated protein kinase phosphorylation site (S274) in NeuroD1 significantly increased the cytoplasmic level at 20 mM glucose. The rise in NeuroD1-mediated transcription in response to glucose also correlated with the change in sub-cellular localization, a response attenuated by PD98059. The data strongly suggest that glucose-stimulation of the MEK–ERK signalling pathway influences NeuroD1 activity at least partially through effects on sub-cellular localization.
【 授权许可】
Unknown
【 预 览 】
Files | Size | Format | View |
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RO201912020312210ZK.pdf | 141KB | download |