Insulin plays a crucial role in the regulation of glucose-homeostasis, and its synthesis is regulated by several stimuli. The transcription of the human insulin gene, enhanced by an elevated intracellular concentration of calcium ions, was completely blocked by Ca2+/calmodulin-dependent protein kinase inhibitor. The activity of the transcription factor activating transcription factor-2 (ATF-2), which binds to the cAMP responsive elements of the human insulin gene, was enhanced by Ca2+/calmodulin-dependent protein kinase IV (CaMKIV). Mutagenesis studies showed that Thr69, Thr71, and Thr73 of ATF-2 are all required for activation by CaMKIV. CaMKIV-induced ATF-2 transcriptional activity was not altered by activation of cJun NH2-terminal protein kinase (JNK) or p38 mitogen-activated protein (MAP) kinase. Furthermore, when transfected into rat primary cultured islets, ATF-2 enhanced glucose-induced insulin promoter activity, whereas cAMP response element-binding protein (CREB) repressed it. These results suggest a mechanism in which ATF-2 regulates insulin gene expression in pancreatic beta-cells, with the transcriptional activity of ATF-2 being increased by an elevated concentration of calcium ions.
Skip Nav Destination
Article navigation
Abstract|
July 01 2000
Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.
N Ban;
N Ban
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Y Yamada;
Y Yamada
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Y Someya;
Y Someya
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Y Ihara;
Y Ihara
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
T Adachi;
T Adachi
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
A Kubota;
A Kubota
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
R Watanabe;
R Watanabe
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
A Kuroe;
A Kuroe
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
A Inada;
A Inada
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
K Miyawaki;
K Miyawaki
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Y Sunaga;
Y Sunaga
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Z P Shen;
Z P Shen
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
T Iwakura;
T Iwakura
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
K Tsukiyama;
K Tsukiyama
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
S Toyokuni;
S Toyokuni
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
K Tsuda;
K Tsuda
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Y Seino
Y Seino
Department of Metabolism and Clinical Nutrition, Graduate School of Medicine, Kyoto University, Japan.
Search for other works by this author on:
Diabetes 2000;49(7):1142–1148
Citation
N Ban, Y Yamada, Y Someya, Y Ihara, T Adachi, A Kubota, R Watanabe, A Kuroe, A Inada, K Miyawaki, Y Sunaga, Z P Shen, T Iwakura, K Tsukiyama, S Toyokuni, K Tsuda, Y Seino; Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.. Diabetes 1 July 2000; 49 (7): 1142–1148. https://doi.org/10.2337/diabetes.49.7.1142
Download citation file: