Present address: Institut für Anatomie, Universität Leipzig, Liebigstraße 13, 04103 Leipzig, Germany.
Early growth response-1 induction by fibroblast growth factor-1 via increase of mitogen-activated protein kinase and inhibition of protein kinase B in hippocampal neurons
Version of Record online: 26 APR 2010
© 2010 The Authors. Journal compilation © 2010 The British Pharmacological Society
British Journal of Pharmacology
Volume 160, Issue 7, pages 1621–1630, August 2010
How to Cite
Benz, A. H., Shajari, M., Peruzki, N., Dehghani, F. and Maronde, E. (2010), Early growth response-1 induction by fibroblast growth factor-1 via increase of mitogen-activated protein kinase and inhibition of protein kinase B in hippocampal neurons. British Journal of Pharmacology, 160: 1621–1630. doi: 10.1111/j.1476-5381.2010.00812.x
- Issue online: 6 JUL 2010
- Version of Record online: 26 APR 2010
- Received 18 August 2009; revised 8 January 2010; accepted 25 February 2010
Background and purpose: The transcription factor early growth response-1 (Egr-1) and the acidic fibroblast growth factor (FGF-1) are involved in many regulatory processes, including hippocampus-associated learning and memory. However, the intracellular signalling mechanisms regulating Egr-1 in hippocampal cells are not entirely understood.
Experimental approach: We used primary mouse hippocampal neurons and the mouse hippocampal neuronal cell line HT22 to investigate how FGF-1 transiently induces Egr-1 protein. This was accomplished by a range of techniques including Western blotting, immunofluorescence, specific protein kinase inhibitors and transfectable constitutively active protein kinase constructs.
Key results: Protein kinase B (PKB) and mitogen-activated protein kinase (MAPK) were both initially phosphorylated and activated by FGF-1 treatment, but when phosphorylated MAPK reached maximal activation, phosphorylated PKB was at its lowest levels, suggesting an interaction between MAPK kinase (MEK-1/2) and phosphatidyl inositol-3-kinase (PI3K) during Egr-1 induction. Interestingly, pharmacological inhibition of MEK-1/2 resulted in a robust increase in the phosphorylation of PKB, which was repressed in the presence of increasing doses of a PI3K inhibitor. FGF-1-mediated Egr-1 induction was impaired by inhibition of MEK-1/2, but not of PI3K. However, elevated levels of PKB, induced by transfection of constitutively active PKB (myrAkt) into hippocampal neuronal HT22 cells, led to reduced levels of Egr-1 after FGF-1 application.
Conclusions and implications: Our data indicate a contribution of inactive (dephosphorylated) PKB to FGF-1-mediated induction of Egr-1, and strongly suggest a functionally and pharmacologically interesting cross-talk between MEK-1/2 and PI3K signalling in hippocampal neurons after FGF-1 stimulation that may play a role in hippocampal synaptic plasticity.