Co-requirement of Cyclic AMP- and Calcium-dependent Protein Kinases for Transcriptional Activation of Cholecystokinin Gene by Protein Hydrolysates

作者：Jean‐Claude Gevrey, Martine Cordier–Bussat, Éric Némoz-Gaillard, Jean‐Alain Chayvialle, Jacques Abello · 发表于：Journal of Biological Chemistry · 年份：2002 · DOI：10.1074/jbc.m201624200 · 被引用次数：31 · 研究领域：Growth Hormone and Insulin-like Growth Factors、Metabolism, Diabetes, and Cancer、Pancreatic function and diabetes

Little is known about the mechanisms by which protein-derived nutrients regulate hormone gene expression in the intestine. We have previously reported that protein hydrolysates (i.e. peptones), which are representative of the protein fraction in the lumen, increased cholecystokinin (CCK) gene transcription in the STC-1 enteroendocrine cell line. In the present work, we examined the intracellular events evoked by peptones to stimulate CCK gene transcription. In STC-1 cells, peptones stimulated cyclic AMP production and protein kinase A (PKA) activity. This was associated with a nuclear translocation of the PKA catalytic subunit and with a PKA-dependent phosphorylation of the CRE-binding protein (CREB) at Ser(133). Using transient transfection experiments and reporter luciferase assays, we show that peptone-stimulated transcriptional activity of the CCK gene promoter was significantly decreased when the PKA pathway was inhibited. Furthermore, the intracellular calcium chelator 1,2-bis-(O-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-tetra(acetoxymethyl)ester completely inhibited peptone-induced stimulation of the CCK gene promoter activity, phosphorylation of CREB, and PKA activity. Peptones increased, in a calcium-dependent manner, the phosphorylation of extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and the MEK inhibitor PD98059 decreased the peptone-induced stimulation of CCK gene promoter activity. This stimulation was also reduced by 30% in the presence o...