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Molecular Mechanisms of Gastrin‐Dependent Gene Regulation
Author(s) -
HÖCKER MICHAEL
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1294.010
Subject(s) - gastrin , gene , chemistry , microbiology and biotechnology , genetics , biology , biochemistry , secretion
A bstract : 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 histidine decarboxylase (HDC) , vesicular monoamine transporter 2 (VMAT2) , and chromogranin A (CgA) 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 cis ‐ and trans ‐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 HDC , VMAT2 , and CgA genes during a secretory challenge of ECL cells by gastrin and possibly other acid secretagogues.