Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster
文献类型：期刊论文
| 作者 | Yu, Yue; Sun, Ying; He, Shengqi; Yan, Cheng; Rui, Liangyou; Li, Wenjun; Liu, Yong（刘勇）
|
| 刊名 | MOLECULAR AND CELLULAR BIOLOGY
 |
| 出版日期 | 2012 |
| 卷号 | 32期号:18页码:3610-3623 |
| 通讯作者 | Liu, Y (reprint author), Chinese Acad Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. |
| 英文摘要 | The Cbl family proteins function as both E3 ubiquitin ligases and adaptor proteins to regulate various cellular signaling events, including the insulin/insulin-like growth factor 1 (IGF1) and epidermal growth factor (EGF) pathways. These pathways play essential roles in growth, development, metabolism, and survival. Here we show that in Drosophila melanogaster, Drosophila Cbl (dCbl) regulates longevity and carbohydrate metabolism through downregulating the production of Drosophila insulin-like peptides (dILPs) in the brain. We found that dCbl was highly expressed in the brain and knockdown of the expression of dCbl specifically in neurons by RNA interference increased sensitivity to oxidative stress or starvation, decreased carbohydrate levels, and shortened life span. Insulin-producing neuron-specific knockdown of dCbl resulted in similar phenotypes. dCbl deficiency in either the brain or insulin-producing cells upregulated the expression of dilp genes, resulting in elevated activation of the dILP pathway, including phosphorylation of Drosophila Akt and Drosophila extracellular signal-regulated kinase (dERK). Genetic interaction analyses revealed that blocking Drosophila epidermal growth factor receptor (dEGFR)-dERK signaling in pan-neurons or insulin-producing cells by overexpressing a dominant-negative form of dEGFR abolished the effect of dCbl deficiency on the upregulation of dilp genes. Furthermore, knockdown of c-Cbl in INS-1 cells, a rat beta-cell line, also increased insulin biosynthesis and glucose-stimulated secretion in an ERK-dependent manner. Collectively, these results suggest that neuronal dCbl regulates life span, stress responses, and metabolism by suppressing dILP production and the EGFR-ERK pathway mediates the dCbl action. Cbl suppression of insulin biosynthesis is evolutionarily conserved, raising the possibility that Cbl may similarly exert its physiological actions through regulating insulin production in beta cells. |
| 类目[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 研究领域[WOS] | Biochemistry & Molecular Biology ; Cell Biology |
| 关键词[WOS] | PANCREATIC BETA-CELLS ; GROWTH-FACTOR RECEPTOR ; C-CBL ; EGF-RECEPTOR ; TYROSINE PHOSPHORYLATION ; LIFE-SPAN ; GLUCOSE-HOMEOSTASIS ; NEGATIVE REGULATORS ; ENERGY-EXPENDITURE ; SIGNALING PATHWAYS |
| 收录类别 | SCI |
| 语种 | 英语 |
| WOS记录号 | WOS:000308416600001 |
| 公开日期 | 2015-12-24 |
| 版本 | 出版稿 |
| 源URL | [http://202.127.25.144/handle/331004/282]  |
| 专题 | 中国科学院上海生命科学研究院营养科学研究所_糖脂代谢与调控研究组 |
| 推荐引用方式 GB/T 7714 | Yu, Yue,Sun, Ying,He, Shengqi,et al. Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster[J]. MOLECULAR AND CELLULAR BIOLOGY,2012,32(18):3610-3623. |
| APA | Yu, Yue.,Sun, Ying.,He, Shengqi.,Yan, Cheng.,Rui, Liangyou.,...&Liu, Yong.(2012).Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster.MOLECULAR AND CELLULAR BIOLOGY,32(18),3610-3623. |
| MLA | Yu, Yue,et al."Neuronal Cbl Controls Biosynthesis of Insulin-Like Peptides in Drosophila melanogaster".MOLECULAR AND CELLULAR BIOLOGY 32.18(2012):3610-3623. |
入库方式： OAI收割
来源：上海营养与健康研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。