Insulin-induced expression of the activity-regulated cytoskeleton-associated gene (ARC) in human neuroblastoma cells requires p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and src tyrosine kinases but is protein kinase C-independent.

We examined the effect of insulin on the expression of the activity-regulated cytoskeleton-associated gene (ARC), an effector immediate early gene with a proposed role in memory formation. In human SH-SY5Y neuroblastoma cells, application of insulin leads to dramatic increase in ARC mRNA and protein levels. Inhibition experiments reveal, that p21(ras), mitogen-activated protein kinase/extracellular regulated kinase and tyrosine kinase (src) activity are required for the insulin-induced ARC expression in SH-SY5Y cells, whereas protein kinase C is not involved in the signal transduction pathway. Our data indicated for the first time a correlation of the insulin-controlled signal cascade and the induction of synaptic plasticity-associated immediate early genes.