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Is stimulation with forskolin equivalent to NGF stimulation?
Asked on Jul 11 2006
Thank you for your enquiry. Forskolin is a compound that activates the cAMP/PKA-dependent signaling pathway; it activates adenylate cyclase and hence elevates intracellular levels of the second messenger cAMP. cAMP controls metabolism, the cytoskeleton and gene expression, and thereby regulates cell fate and also more specialized cellular functions, such as muscle contraction and memory. (very complex pathway) NGF binds to its receptor (RTK family) which triggers the ras/raf/MEK/ERK cascade, resulting in the activation of multiple protein kinases. Some of these kinases translocate to the nucleus to activate transcriptional activators, such as CREB. ERK signalling plays an important role in determining cell fate, choosing between diverse responses such as proliferation, differentiation, senescence or survival and it also regulates specialist functions such as those in neurones and immune cells. This ras-based component of the NGF pathway is primarily responsible for inducing and maintaining differentiation of NGF-sensitive neurons. These two pathways are thought to interact through the regulation of the RAF family of kinases by cAMP. So, in some cases Forskolin and NGF are used in different experiments to trigger different effects, in some cases, they are used together (forskolin enhances NGF action) and in some experiments you can use NGF or forskolin to see the same effects. The PC12 pheochromocytoma cell line responds to NGF by undergoing growth arrest and proceeding to differentiate toward a neuronal phenotype. Similar effect can be seen with forskolin. I hope this information helps. Please do not hesitate to contact us if you need anything further.
Abcam Scientific Support
Answered on Jul 13 2006