Transcriptional activation of the rat vesicular monoamine transporter 2 promoter in gastric epithelial cells - Regulation by gastrin

Vesicular monoamine transporter 2 is important for the accumulation of mono amine neurotransmitters into synaptic vesicles and histamine transport into secretory vesicles of the enterochromaffin like cell of the gastric corpus . In this study we have investigated the mechanisms regulating the transcri ptional activation of the rat vesicular monoamine transporter 2 (VMAT2) pro moter in gastric epithelial cells. Maintenance of basal levels of transcrip tion was dependent on the presence of SP1, cAMP-response element (CRE), and overlapping AP2/SP1 consensus sequences within the region of promoter from -86 to +1 base pairs (bp), Gastrin stimulation increased transcriptional a ctivity, and responsiveness was shown to be dependent on the CRE (-33 to -2 6 bp) and AP2/SP1 (-61 to -48 bp) consensus sites but independent of the SP 1 site at -86 to -81 bp. Gastrin-induced transcription was dependent on the cooperative interaction of an uncharacterized nuclear factor of similar to 23.3 kDa that bound to the putative AP2/SP1 site, CRE-binding protein (CRE B), and CREE-binding protein/ p300, Gastrin stimulation resulted in the inc reased binding of phosphorylated CREB to the promoter, but it did not resul t in the increased binding of the AP2/SP1-binding protein. The gastrin resp onsiveness of the promoter was shown to be dependent on both the protein ki nase C and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase-signaling pathways, which may converge on the AP2/SP1-binding protein.