Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth factors coordinately regulate a variety of different genes to stimulate cellular proliferation. In the stomach, gastrin, epidermal growth factor (EGF), and transforming growth factor-alpha all mediate gastric mucosal homeostasis by promoting cell renewal. We have previously shown that EGF and phorbol esters stimulate the human gastrin promoter through a novel GC-rich DNA element 5'-(68)GGGGCGGGGTGGGGGG-53 called gERE (gastrin EGF response element). In this report, we show that three factors bind to this element, the transcription factor Sp1 and two fast migrating complexes designated gastrin EGF response proteins (gERP 1 and 2). To understand how these factors bind and confer EGF responsiveness, mutations of gERE were tested in vitro for protein binding and in vivo for promoter activation. Both gel shift assays and UV cross-linking studies revealed that the factors bind to overlapping domains, Sp1 to the 5' half-site and gERP 1 and 2 to the 3' half-site. Placing either the 5' or 3' mutations upstream of a minimal gastrin promoter abolished EGF induction. Therefore both the 5' and 3' domains were required to confer EGF induction. Collectively, these results demonstrate that complex interactions between Sp1 and other factors binding to overlapping gERE half-sites confer EGF responsiveness to the gastrin promoter.
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PMID:Epidermal growth factor stimulation of the human gastrin promoter requires Sp1. 789 Jul 69

Epidermal growth factor (EGF) and phorbol esters stimulate the human gastrin promoter through a novel GC-rich DNA element 5'-68GGGGCGGGGTGGGGGG-53 called gERE (gastrin EGF response element). The transcription factor Sp1 and two fast migrating complexes designated gastrin EGF response proteins (gERP1 and gERP2) bind to gERE. Sp1 binds to the 5' half site and gERP bind to the 3' half site. Both the 5' and 3' domains and some overlap between the two domains are required to confer EGF induction. Complex interactions between Sp1 and other factors binding to overlapping gERE half-sites confer EGF responsiveness to the gastrin promoter.
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PMID:[The transcriptional regulation of the human gastrin gene by EGF]. 892 Jun 79

Gastrin release from the antral gastrin-expressing cell (G cell) is regulated by bombesin and luminal factors. Yet, these same extracellular regulators do not stimulate expression of the gene. Since the gastric mucosa expresses large quantities of EGF receptor ligands such as TGFalpha, we examined whether EGF receptor ligands stimulate gastrin gene expression in gastrin-expressing cell cultures. EGF receptor activation of primary cultures stimulated gastrin gene expression about twofold; whereas bombesin treatment of antral G cell cultures stimulated gastrin release but not gene expression. EGF and TGFalpha were weak stimulants of gastrin release. EGF receptor activation of AGS human gastric adenocarcinoma cell line stimulated gastrin gene expression nearly fourfold; and gastrin reporter constructs transfected into AGS cells were stimulated more than fourfold by EGF. EGF induction was conferred by the previously defined GC-rich gastrin EGF response element (gERE) element located at -68 to -53 bp upstream from the cap site since a mutation of the gERE element abolished both basal and EGF induction. Moreover, EGF treatment of AGS cells stimulated binding of the transcription factor Sp1 to this element. Collectively, these results demonstrate that gastrin gene expression and gastrin release are regulated by different signaling pathways: gene expression by EGF receptor activation and gastrin secretion by neuropeptides and luminal factors.
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PMID:EGF receptor activation stimulates endogenous gastrin gene expression in canine G cells and human gastric cell cultures. 916 7