Insulin signalling is well studied in peripheral tissue, but not in neuronal tissue. To gain more insight into neuronal insulin signalling we examined protein kinase B (PKB) and extracellular regulated kinase 1 and 2 ( @entity8837 ) regulation in serum-deprived Neuro2a cells. Insulin phosphorylated PKB in a dose-dependent manner but reduced phosphorylation of @entity8837 . Both processes were @entity4357 3-kinase ( @entity3115 ) dependent. Interestingly, blockade of @entity3115 in combination with insulin induced phosphorylation of @entity8837 . The phosphorylation of @entity8837 could be blocked with a specific inhibitor of @entity13438 ( @entity13438 ), suggesting that it was mediated through the highly conserved Ras-Raf- @entity13438 - @entity8837 pathway. Prolonged exposure to high concentrations of insulin resulted in a desensitized @entity3115 -PKB route. The insulin-induced inhibition of @entity8837 phosphorylation was also diminished when the @entity3115 -PKB route was desensitized. Blockade of @entity3115 in combination with insulin, however, still resulted in an unaltered @entity13438 -dependent phosphorylation of @entity8837 . We conclude that @entity3115 is an important integrator of insulin signalling in Neuro2a cells as it regulates activation of PKB and inhibition of @entity8837 , and is sensitive to the duration of the insulin stimulus.

Insulin inhibits extracellular regulated kinase 1/2 phosphorylation in a XXXX 3-kinase (PI3) kinase-dependent manner in Neuro2a cells.

@entity3115 :: ('18708(Tax:10090)', 'Gene') :: ['PI3K'] @entity13438 :: ('17242(Tax:10090)', 'Gene') :: ['MEK', 'mitogen-activated protein/ERK kinase'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity8837 :: ('26417;26413', 'Gene') :: ['ERK1/2']
@entity4357 :: (MESH:D010716,Chemical) :: ['phosphatidylinositol']
