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Glucose induced MAPK signalling influences NeuroD1‐mediated activation and nuclear localization
Author(s) -
Petersen Helle V,
Jensen Jan N,
Stein Roland,
Serup Palle
Publication year - 2002
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(02)03318-5
Subject(s) - mapk/erk pathway , transcription factor , microbiology and biotechnology , chemistry , phosphorylation , serine , kinase , mek inhibitor , mitogen activated protein kinase , biology , biochemistry , gene
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.