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

Minseon Park, Bok Soon Lee, Soung Hoo Jeon, Hyun Ja Nam, Gwang Lee, Chul Ho Kim, Hyeseong Cho, Jae Ho Lee

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1804-1817
Number of pages14
JournalJournal of Biological Chemistry
Volume290
Issue number3
DOIs
StatePublished - Jan 16 2015

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'A novel isoform of met receptor tyrosine kinase blocks hepatocyte growth factor/met signaling and stimulates skeletal muscle cell differentiation'. Together they form a unique fingerprint.

Cite this