Description:
<jats:p><jats:bold>A<jats:sc>bstract</jats:sc>: </jats:bold> The peptide hormone gastrin is the key regulator of gastric acid secretion. Gastrin exerts its effects as acid secretagogue through functional activation of gastric enterochromaffin‐like (ECL) cells, which control acid secretion through biosynthesis and release of histamine. In ECL cells, concerted activation of <jats:italic>histidine decarboxylase (HDC)</jats:italic>, <jats:italic>vesicular monoamine transporter 2 (VMAT2)</jats:italic>, and <jats:italic>chromogranin A (CgA)</jats:italic> genes by gastrin is a prerequisite for proper acid control. To elucidate the molecular pathways underlying gastrin‐dependent control of ECL cell genes, we recently analyzed the signaling cascades, regulatory promoter elements, and transcription factors mediating the transcriptional effects of gastrin. Our studies identified the Raf>MEK1>ERK 1/‐2 kinase module as the common signaling pathway mediating gastrin‐dependent ECL cell gene transcription. In contrast to this uniform signaling cascade, pronounced heterogeneity was detected between <jats:italic>cis</jats:italic>‐ and <jats:italic>trans</jats:italic>‐activating regulatory factors conferring gastrin responsiveness. The molecular diversity of transcription factors and regulatory enhancer elements transmitting gastrin‐triggered gene transcription offers the molecular basis for synergistic, but differential, regulation of <jats:italic>HDC</jats:italic>, <jats:italic>VMAT2</jats:italic>, and <jats:italic>CgA</jats:italic> genes during a secretory challenge of ECL cells by gastrin and possibly other acid secretagogues.</jats:p>