Alpha2-adrenergic receptor subtype-specific activation of NF-kappaB in PC12 cells.
In the present study we sought to investigate the signal transduction mechanisms that underlie the alpha2-adrenergic receptor (AR)-induced, subtype-specific neuronal differentiation of PC12 cells. Alpha2-ARs induced NF-kappaB transcriptional activity and p21(waf-1) gene transcription in the same subtype-specific manner (alpha2A<alpha2B<alpha2C) as the neuronal differentiation induced by these receptors. Following pretreatment with the MEK1 inhibitor PD98059, the NF-kappaB response to epinephrine becomes uniform with loss of subtype specificity. In contrast, there is complete abolishment of epinephrine-induced transcription by NF-kappaB after pretreatment with the PI3-K inhibitor LY294002. These data imply that induction of transcription by NF-kappaB is PI-3K-dependent; however, the subtype-specific induction of transcription by NF-kappaB is ERK1/2-dependent. Taken together, these results suggest that the three alpha2-adrenoceptors promote an interaction between PI-3K and ERK1/2 in a subtype-specific way, leading to subtype-specific induction of transcription by NF-kappaB and p21(waf-1) gene transcription, which might underlie the subtype-specific differentiation of PC12 cells induced by these receptors.
Lymperopoulos
Anastasios
A
Center for Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Karkoulias
Georgios
G
Koch
Walter J
WJ
Flordellis
Christodoulos S
CS
D000818:Animals; D002454:Cell Differentiation; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D051381:Rats; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology*; D015398:Signal Transduction; D014158:Transcription, Genetic
C547768:ADRA2A protein, human; C547771:ADRA2B protein, human; C547774:ADRA2C protein, human; C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016328:NF-kappa B; D018341:Receptors, Adrenergic, alpha-2; D019869:Phosphatidylinositol 3-Kinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3