Induction of the SHARP-2 mRNA level by insulin is mediated by multiple signaling pathways
Autor: | Kazuya Yamada, Takashi Tanaka, Yukiko Kanai, Ayumi Haneishi, Akiko Tsukada, Kosuke Asano, Moe Ono, Katsuhiro Takagi, Yoshiko Komatsu, Koji Tomita |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Transcription Genetic medicine.medical_treatment Applied Microbiology and Biotechnology Biochemistry Analytical Chemistry 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Insulin receptor substrate Basic Helix-Loop-Helix Transcription Factors medicine Animals Insulin RNA Messenger Enhancer Molecular Biology Transcription factor Protein Kinase C Protein kinase C PI3K/AKT/mTOR pathway Homeodomain Proteins Phosphoinositide 3-kinase biology TOR Serine-Threonine Kinases Organic Chemistry General Medicine Molecular biology Rats Isoenzymes Insulin receptor 030104 developmental biology 030220 oncology & carcinogenesis biology.protein Signal Transduction Biotechnology |
Zdroj: | Bioscience, Biotechnology, and Biochemistry. 81:256-261 |
ISSN: | 1347-6947 0916-8451 |
DOI: | 10.1080/09168451.2016.1249450 |
Popis: | The rat enhancer of split- and hairy-related protein-2 (SHARP-2) is an insulin-inducible transcription factor which represses transcription of the rat phosphoenolpyruvate carboxykinase gene. In this study, a regulatory mechanism of the SHARP-2 mRNA level by insulin was analyzed. Insulin rapidly induced the level of SHARP-2 mRNA. This induction was blocked by inhibitors for phosphoinositide 3-kinase (PI 3-K), protein kinase C (PKC), and mammalian target of rapamycin (mTOR), actinomycin D, and cycloheximide. Whereas an adenovirus infection expressing a dominant negative form of atypical PKC lambda (aPKCλ) blocked the insulin-induction of the SHARP-2 mRNA level, insulin rapidly activated the mTOR. Insulin did not enhance transcriptional activity from a 3.7 kb upstream region of the rat SHARP-2 gene. Thus, we conclude that insulin induces the expression of the rat SHARP-2 gene at the transcription level via both a PI 3-K/aPKCλ- and a PI 3-K/mTOR- pathways and that protein synthesis is required for this induction. |
Databáze: | OpenAIRE |
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