ISSN:
1471-4159
Quelle:
Blackwell Publishing Journal Backfiles 1879-2005
Thema:
Medizin
Notizen:
Abstract: Transcriptional responses to growth factor and G protein-coupled receptors were compared in PC12 cells using retroviral luciferase reporters. In cells stably expressing α1A-adrenergic receptors, norepinephrine activated all five reporters [AP1 (activator protein-1), SRE (serum response element), CRE (cyclic AMP response element), NFκB) (nuclear factor-κB), and NFAT (nuclear factor of activated T cells)], whereas nerve growth factor (NGF) and epidermal growth factor activated only AP1 and SRE. Activation of P2Y2 receptors by UTP did not activate any reporters. Protein kinase C inhibition blocked NFκB activation by norepinephrine, but potentiated CRE. Mitogen-activated protein kinase kinase inhibition blocked AP1 activation by norepinephrine, but also potentiated CRE. p38 mitogen-activated protein kinase inhibition reduced most norepinephrine responses, but not NGF responses. inhibition of Src eliminated SRE responses to norepinephrine and NGF, and reduced all responses except CRE. Phosphatidylinositol 3-kinase inhibitors markedly potentiated CRE activation by norepinephrine, with only small effects on the other responses. Comparison of the three human subtypes showed that the α1A activated all five reporters, the α1B showed smaller effects, and the α1D was ineffective. Cell differentiation caused by norepinephrine, but not NGF, was reduced by all inhibitors studied. These experiments suggest that α1A-adrenergic receptors activate a wider array of transcriptional responses than do growth factors in PC12 cells. These responses are not linearly related to second messenger production, and different subtypes show different patterns of activation.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1046/j.1471-4159.2000.0742392.x
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