Differential signaling cascade of MAP kinase and S6 kinase depends on 3',5'-monophosphate concentration in Schwann cells: Correlation to cellular differentiation and proliferation

Schwann cells produce myelin in the peripheral nervous system (PNS) and play an important role in the maintenance of the normal function of PNS. Our previous studies have shown that derivatives of adenosine 3',5'- monophosphate (cAMP) can regulate the cell-fate (i.e., proliferation and differentiation into cell surface galactocerebroside-positive cells) depending on its concentration in vitro. Higher concentration of cAMP can induce the expression of cell surface galactocerebroside, while proliferation can be induced by lower concentration of cAMP. However, the detailed molecular mechanism of how the same second messenger yields different phenotypes of Schwann cells depending on its concentration remains to be elucidated. Here we show that low concentration of 8-bromo cAMP, a cell- permeable derivative of cAMP, activates S6 kinase activity with a short- lived activation of mitogen-activated protein kinase (MAPK), whereas high dose of the reagent activates S6 kinase much less than that of low dose with a small and prolonged activation of MAPK in Schwann cells. These data clearly demonstrated that a rise in the intracellular cAMP uses the MAPK-S6 kinase pathway as an intracellular sinaling cascade and different magnitude and duration of the activation of this pathway might underlie the different cellular fate depending on the intensity of the stimulation.