期刊
JOURNAL OF CELL BIOLOGY
卷 163, 期 5, 页码 931-936出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.200307158
关键词
IGF; rapamycin; skeletal muscle differentiation; PI3K; Akt
类别
资金
- NIAMS NIH HHS [R01 AR048914, AR48914] Funding Source: Medline
- NIGMS NIH HHS [GM58064, R01 GM058064] Funding Source: Medline
Insulin-like growth factors (IGFs) are essential for skeletal muscle development, regeneration, and hypertrophy. Although autocrine actions of IGF-II are known to initiate myoblast differentiation, the regulatory elements and upstream signaling pathways for myogenic expression of IGF-II remain elusive. Here, we report the regulation of IGF-II transcription by mTOR, as well as by amino acid sufficiency, through the IGF-II promoter 3 and a downstream enhancer during C2C12 myoblast differentiation. Furthermore, we present evidence that IGF production, and not IGF signaling, is the primary target for mTORs function in the initiation of differentiation. Moreover, myogenic signaling by mTOR is independent of its kinase activity and mediated by the PI3K-Akt pathway. Our findings represent the first identification of a signaling pathway that regulates IGF-II expression in myogenesis and implicate the mTOR-IGF axis as a molecular link between nutritional levels and skeletal muscle development.
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