Mechanisms of activin signaling in neuroblastoma cells

Activin, a member of the TGF-beta superfamily. affects the expression of certain neuropeptides in populations of parasympathetic and sympathetic neu rons. We used a human neuroblastoma cell line, NBFL, as a model to examine the mechanisms of activin signaling in cells of neural lineage. In NBFL colls, activin induces transcription of the gene encoding the neuropeptide vasoactiw intestinal peptide (VIP) through a 180bp region of the VIP promoter. This> region also mediates the transcriptional activation of the VIP gene by the neu ropoietic cytokines. The molecular mechanisms through which activin elicits induction of VIP gene transcription are unknown. Recently, activin was shown to activate a new family of transcription factors, the Smad proteins. Smad proteins interact with receptors at the cell surface, are phosphorylated by the activated receptor, whereupon they dimerize and translocate to the nucleus to activate transcription. However, the expression and activity of Smad proteins in cells of neural lineage has not yet been reported. In order to investigate the possible involvement of Smad proteins in activin regulation of VIP gene exprès sion, we have looked for expression and activation of Smad proteins in BFL ceils. Western blots, using an antibody cross reactive with both Smad 2 and 3. indicate the presence of Smad proteins in NBFI, cells. Activin treatment of NBFL cells induces translocation of these proteins to the nucleus within 15 minutes. Experiments to determine the involvement of Smad proteins in activin mediated induction of VIP gene transcription are tonlinuing.