Hansen Thomas v O, Rehfeld Jens F, Nielsen Finn C
Department of Clinical Biochemistry, University Hospital Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Neuroreport. 2004 Apr 9;15(5):841-5. doi: 10.1097/00001756-200404090-00021.
The cAMP signaling pathway stimulates cholecystokinin (CCK) gene transcription via CREB binding to a cAMP response element (CRE). In the present study we examined the function of glycogen synthase kinase-3beta (GSK-3beta) on cAMP-induced CCK gene transcription. Co-transfection of GSK-3beta reduced the cAMP-induced CCK promoter activity with approximately 80% and approximately 60% in SK-N-MC and PC12 cells, respectively. Binding of in vitro translated CREB to the CCK CRE(-80) promoter element was reduced following incubation with recombinant GSK-3beta. Finally, mutation of serine-129, which is a phosphorylation site for GSK-3beta, did not abolish cAMP-induced CREB-dependent transcription, and cAMP-mediated GAL4-CREB transcription was unaffected by co-transfection with GSK-3beta. We conclude that GSK-3beta regulates cAMP-induced CCK transcription by reducing CREB binding to the CRE(-80) element in the CCK promoter.
环磷酸腺苷（cAMP）信号通路通过环磷腺苷效应元件结合蛋白（CREB）与环磷腺苷反应元件（CRE）结合来刺激胆囊收缩素（CCK）基因转录。在本研究中，我们检测了糖原合酶激酶-3β（GSK-3β）对cAMP诱导的CCK基因转录的作用。共转染GSK-3β分别使SK-N-MC和PC12细胞中cAMP诱导的CCK启动子活性降低了约80%和约60%。用重组GSK-3β孵育后，体外翻译的CREB与CCK CRE（-80）启动子元件的结合减少。最后，作为GSK-3β磷酸化位点的丝氨酸-129突变并未消除cAMP诱导的CREB依赖性转录，并且cAMP介导的GAL4-CREB转录不受与GSK-3β共转染的影响。我们得出结论，GSK-3β通过减少CREB与CCK启动子中CRE（-80）元件的结合来调节cAMP诱导的CCK转录。
