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Muscarinic receptor‐mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells
Author(s) -
Greenwood Jeffrey M.,
Dragunow Michael
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00992.x
Subject(s) - creb , carbachol , phosphorylation , muscarinic acetylcholine receptor , endocrinology , cyclic amp response element binding protein , biology , creb binding protein , cholinergic , egr1 , muscarinic acetylcholine receptor m4 , immediate early gene , ltp induction , medicine , long term potentiation , chemistry , microbiology and biotechnology , transcription factor , receptor , stimulation , biochemistry , gene expression , gene
This study describes the effect of signalling through muscarinic acetylcholine receptors on two transcription factors implicated in long‐term synaptic plasticity and memory formation, EGR1 and the cyclic AMP response element binding protein (CREB). In SK‐N‐SH neuroblastoma cells, treatment with the cholinergic agonist carbachol led to maximal induction of EGR1 1 h after stimulation. This was preceded by the phosphorylation of CREB, which peaked as early as 5 minutes after carbachol treatment. The levels of both EGR1 and phosphorylated CREB (pCREB) slowly decayed over 4–8 h. CREB phosphorylation and EGR1 induction showed similar sensitivity to carbachol concentration, with EC 50 values in the range of 1–10 µ M , and the changes in both transcription factors were blocked by the muscarinic antagonist atropine. As has been described elsewhere, EGR1 induction was dependent on activation of p42/44 MAP kinase, as it was blocked by the MEK inhibitor U0126. However, CREB phosphorylation by carbachol was largely unaffected by MAP kinase blockade. As both CREB phosphorylation and EGR1 induction have been linked to long‐term potentiation and some forms of memory consolidation, these results may implicate CREB and EGR1 in independent or partially independent cholinergic signalling pathways involved in memory processes.