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A novel isoform of met receptor tyrosine kinase blocks hepatocyte growth factor/Met signaling and stimulates skeletal muscle cell differentiation.

Authors
Park, M | Lee, BS  | Jeon, SH | Nam, HJ | Lee, G  | Kim, CH  | Cho, H  | Lee, JH
Citation
The Journal of biological chemistry, 290(3). : 1804-1817, 2015
Journal Title
The Journal of biological chemistry
ISSN
0021-92581083-351X
Abstract
Hepatocyte growth factor (HGF) and its receptor, Met, regulate skeletal muscle differentiation. In the present study, we identified a novel alternatively spliced isoform of Met lacking exon 13 (designated Δ13Met), which is expressed mainly in human skeletal muscle. Alternative splicing yielded a truncated Met having extracellular domain only, suggesting an inhibitory role. Indeed, Δ13Met expression led to a decrease in HGF-induced tyrosine phosphorylation of Met and ERK phosphorylation, as well as cell proliferation and migration via sequestration of HGF. Interestingly, in human primary myoblasts undergoing differentiation, Δ13Met mRNA and protein levels were rapidly increased, concomitantly with a decrease in wild type Met mRNA and protein. Inhibition of Δ13Met with siRNA led to a decreased differentiation, whereas its overexpression potentiated differentiation of human primary myoblasts. Furthermore, in notexin-induced mouse injury model, exogenous Δ13Met expression enhanced regeneration of skeletal muscle, further confirming a stimulatory role of the isoform in muscle cell differentiation. In summary, we identified a novel alternatively spliced inhibitory isoform of Met that stimulates muscle cell differentiation, which confers a new means to control muscle differentiation and/or regeneration.
MeSH

DOI
10.1074/jbc.M114.596957
PMID
25471370
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Otolaryngology
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
Ajou Authors
김, 철호  |  이, 광  |  이, 복순  |  이, 재호  |  조, 혜성
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