title: The mammalian target of rapamycin signaling pathway regulates myocyte enhancer factor-2C phosphorylation levels through integrin-linked kinase in goat skeletal muscle satellite cells.
abstract: Mammalian target of rapamycin (mTOR) signaling pathway plays a key role in muscle development and is involved in multiple intracellular signaling pathways. Myocyte enhancer factor-2 (MEF2) regulates muscle cell proliferation and differentiation. However, how the mTOR signaling pathway regulates MEF2 activity remains unclear. We isolated goat skeletal muscle satellite cells (gSSCs) as model cells to explore mTOR signaling pathway regulation of MEF2C. We inhibited mTOR activity in gSSCs with PP242 and found that MEF2C phosphorylation was decreased and that muscle creatine kinase (MCK) expression was suppressed. Subsequently, we detected integrin-linked kinase (ILK) using MEF2C coimmunoprecipitation; ILK and MEF2C were colocalized in the gSSCs. We found that inhibiting mTOR activity increased ILK phosphorylation levels and that inhibiting ILK activity with Cpd 22 and knocking down ILK with small interfering RNA increased MEF2C phosphorylation and MCK expression. In the presence of Cpd 22, mTOR activity inhibition did not affect MEF2C phosphorylation. Moreover, ILK dephosphorylated MEF2C in vitro. These results suggest that the mTOR signaling pathway regulates MEF2C positively and regulates ILK negatively and that ILK regulates MEF2C negatively. It appears that the mTOR signaling pathway regulates MEF2C through ILK, further regulating the expression of muscle-related genes in gSSCs.
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Haiqing
authors.initials: H
authors.lastname: Wu
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ren
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Pan
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Zhenguo
authors.initials: Z
authors.lastname: Dong
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Cang
authors.affiliation: Key Laboratory of Mammalian Reproductive Biology and Biotechnology Ministry of Education, Inner Mongolia University, China.
authors.forename: Dongjun
authors.initials: D
authors.lastname: Liu
mesh_terms: D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D006041:Goats; D064326:MEF2 Transcription Factors / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D032496:Satellite Cells, Skeletal Muscle / Q000201:enzymology / Q000378:metabolism*; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D000099200:Scaffold Protein ILK
chemical_list: D064326:MEF2 Transcription Factors; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D000099200:Scaffold Protein ILK
keywords: ILK; MEF2C; mTOR signaling pathway; regulation; skeletal muscle satellite cells