α₂-Adrenergic receptor subtype-specific activation of NF-κB in PC12 cells

In the present study we sought to investigate the signal transduction mechanisms that underlie the α2-adrenergic receptor (AR)-induced, subtype-specific neuronal differentiation of PC12 cells. α2-ARs induced NF-κB transcriptional activity and p21waf-1 gene transcription in the same subtype-specific manner (α2A < α2B < α2C) as the neuronal differentiation induced by these receptors. Following pretreatment with the MEK1 inhibitor PD98059, the NF-κB response to epinephrine becomes uniform with loss of subtype specificity. In contrast, there is complete abolishment of epinephrine-induced transcription by NF-κB after pretreatment with the PI3-K inhibitor LY294002. These data imply that induction of transcription by NF-κB is PI-3K-dependent; however, the subtype-specific induction of transcription by NF-κB is ERK1/2-dependent. Taken together, these results suggest that the three α2-adrenoceptors promote an interaction between PI-3K and ERK1/2 in a subtype-specific way, leading to subtype-specific induction of transcription by NF-κB and p21waf-1 gene transcription, which might underlie the subtype-specific differentiation of PC12 cells induced by these receptors.