title: A novel isoform of met receptor tyrosine kinase blocks hepatocyte growth factor/Met signaling and stimulates skeletal muscle cell differentiation.
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.
authors.affiliation: From the Departments of Biochemistry and Molecular Biology.
authors.forename: Minseon
authors.initials: M
authors.lastname: Park
authors.affiliation: Otolaryngology, and.
authors.forename: Bok-Soon
authors.initials: BS
authors.lastname: Lee
authors.affiliation: From the Departments of Biochemistry and Molecular Biology.
authors.forename: Soung-Hoo
authors.initials: SH
authors.lastname: Jeon
authors.affiliation: From the Departments of Biochemistry and Molecular Biology.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Nam
authors.affiliation: Physiology, Ajou University School of Medicine, Yeongtong-gu, Suwon 443-721, Korea.
authors.forename: Gwang
authors.initials: G
authors.lastname: Lee
authors.affiliation: Otolaryngology, and.
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Kim
authors.affiliation: From the Departments of Biochemistry and Molecular Biology.
authors.forename: Hyeseong
authors.initials: H
authors.lastname: Cho
authors.affiliation: From the Departments of Biochemistry and Molecular Biology, jhlee64@ajou.ac.kr.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
mesh_terms: D017398:Alternative Splicing; D000818:Animals; D001706:Biopsy; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D017228:Hepatocyte Growth Factor / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000166:cytology*; D032446:Myoblasts / Q000378:metabolism; D041681:NIH 3T3 Cells; D010766:Phosphorylation; D020033:Protein Isoforms / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034622:RNA Interference; D012038:Regeneration; D015398:Signal Transduction
chemical_list: D020033:Protein Isoforms; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Alternative Splicing; Differentiation; Hepatocyte Growth Factor/Scatter Factor (HGF/SF); Met; Receptor Tyrosine Kinase; Skeletal Muscle