Muscarinic receptor-mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells
Version of Record online: 3 JUL 2002
Journal of Neurochemistry
Volume 82, Issue 2, pages 389–397, July 2002
How to Cite
Greenwood, J. M. and Dragunow, M. (2002), Muscarinic receptor-mediated phosphorylation of cyclic AMP response element binding protein in human neuroblastoma cells. Journal of Neurochemistry, 82: 389–397. doi: 10.1046/j.1471-4159.2002.00992.x
- Issue online: 3 JUL 2002
- Version of Record online: 3 JUL 2002
- Received December 6, 2001; revised manuscript received March 28, 2002; accepted April 15, 2002.
- MAP kinase;
- muscarinic acetylcholine receptor
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 EC50 values in the range of 1–10 µM, 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.