α₂-Adrenergic Receptors Activate MAPK via PI-3K Activation and EGF Receptor Transactivation in PC12 Cells

We have previously shown that stimulation of all three α 2-AR subtypes in PC12 cells leads to p42/p44 MAPK (ERK 1/2) activation (1). As an initial effort to delineate the signal transduction mechanisms employed by the α2-ARs for this effect, we investigated the involvement of PI-3K and EGF receptor and found that the activation of MAP kinase by α2-ARs in PC12 cells requires transactivation of the EGF receptor and activation of PI-3K. These results reflect the remarkable diversity of the signal transduction pathways utilized by α2-ARs in order to elicit the critical signaling event of MAPK activation in PC12 cells.