title: Induction of the SHARP-2 mRNA level by insulin is mediated by multiple signaling pathways.
abstract: 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.
authors: a Graduate School of Health Science , Matsumoto University , Matsumoto , Japan.
authors: Yukiko
authors: Y
authors: Kanai
authors: b Faculty of Human Health Science, Department of Health and Nutritional Science , Matsumoto University , Matsumoto , Japan.
authors: Kosuke
authors: K
authors: Asano
authors: a Graduate School of Health Science , Matsumoto University , Matsumoto , Japan.
authors: Yoshiko
authors: Y
authors: Komatsu
authors: a Graduate School of Health Science , Matsumoto University , Matsumoto , Japan.|b Faculty of Human Health Science, Department of Health and Nutritional Science , Matsumoto University , Matsumoto , Japan.
authors: Katsuhiro
authors: K
authors: Takagi
authors: c Faculty of Pharmacy, Laboratory of Molecular Biology , Osaka Ohtani University , Tondabayashi , Japan.
authors: Moe
authors: M
authors: Ono
authors: c Faculty of Pharmacy, Laboratory of Molecular Biology , Osaka Ohtani University , Tondabayashi , Japan.
authors: Takashi
authors: T
authors: Tanaka
authors: c Faculty of Pharmacy, Laboratory of Molecular Biology , Osaka Ohtani University , Tondabayashi , Japan.
authors: Koji
authors: K
authors: Tomita
authors: b Faculty of Human Health Science, Department of Health and Nutritional Science , Matsumoto University , Matsumoto , Japan.
authors: Ayumi
authors: A
authors: Haneishi
authors: b Faculty of Human Health Science, Department of Health and Nutritional Science , Matsumoto University , Matsumoto , Japan.
authors: Akiko
authors: A
authors: Tsukada
authors: a Graduate School of Health Science , Matsumoto University , Matsumoto , Japan.|b Faculty of Human Health Science, Department of Health and Nutritional Science , Matsumoto University , Matsumoto , Japan.
authors: Kazuya
authors: K
authors: Yamada
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis / Q000235:genetics*; D045744:Cell Line, Tumor; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics; D011493:Protein Kinase C / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D000099293:Protein Kinase C-lambda
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D007328:Insulin; D007527:Isoenzymes; D011493:Protein Kinase C; D012333:RNA, Messenger; D058570:TOR Serine-Threonine Kinases; D000099293:Protein Kinase C-lambda; C491538:Bhlhe40 protein, rat
keywords: SHARP-2; atypical protein kinase C lambda; insulin; mammalian target of rapamycin; phosphoinositide 3-kinase