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- Title
Activating transcription factor-2 is a positive regulator in CaM kinase IV-induced human insulin gene expression.
- Authors
Ban, Nobuhiro; Yamada, Yuichiro; Someya, Yoshimichi; Ihara, Yu; Adachi, Tetsuya; Kubota, Akira; Watanabe, Rie; Kuroe, Akira; Inada, Akari; Miyawaki, Kazumasa; Sunaga, Yasuhiro; Shen, Zhen-Ping; Iwakura, Toshio; Tsukiyama, Katsushi; Toyokuni, Shinya; Tsuda, Kinsuke; Seino, Yutaka; Ban, N; Yamada, Y; Someya, Y
- Abstract
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.
- Subjects
TRANSCRIPTION factors; PROTEIN kinases; INSULIN; GENETIC regulation
- Publication
Diabetes, 2000, Vol 49, Issue 7, p1142
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.49.7.1142