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
Rok vydání: 2017
Předmět:
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