Glucose induced MAPK signalling influences NeuroD1‐mediated activation and nuclear localization

FEBS Letters

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