Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy

Satomi Mitsuhashi, Hiroaki Mitsuhashi, Matthew S. Alexander, Hiroyuki Sugimoto, Peter B. Kang

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17 Scopus citations


Recessive mutations in MEGF10 are known to cause a congenital myopathy in humans. Two mutations in the extracellular EGF-like domains of MEGF10, C326R and C774R, were associated with decreased tyrosine phosphorylation of MEGF10 in vitro. Y1030 was identified to be the major tyrosine phosphorylation site in MEGF10 and is phosphorylated at least in part by c-Src. Overexpression of wild-type MEGF10 enhanced C2C12 myoblast proliferation, while overexpression of Y1030F mutated MEGF10 did not. We conclude that MEGF10-mediated signaling via tyrosine phosphorylation helps to regulate myoblast proliferation. Defects in this signaling pathway may contribute to the disease mechanism of MEGF10 myopathy.

Original languageEnglish (US)
Pages (from-to)2952-2957
Number of pages6
JournalFEBS Letters
Issue number18
StatePublished - Sep 17 2013
Externally publishedYes

Bibliographical note

Funding Information:
The authors thank Shoichi Ishiura for generously providing plasmids used in this study. We also thank Lane J. Mahoney, Elicia Estrella, Kyungah Cho, Motoyasu Satou, Chieko Aoyama, Megumu Ogawa, Norio Motohashi, Melissa Wu, Emanuela Gussoni, and Louis M. Kunkel for their helpful comments. SM is supported by the William Randolph Hearst Fund at Harvard Medical School. PBK is supported by Muscular Dystrophy Association (MDA) Research Grant 186796, a Pilot Grant at Boston Children’s Hospital, and NIH R01 NS080929. MSA is supported by Muscular Dystrophy Association (MDA) Development Grant MDA255059. Sanger DNA sequencing experiments were performed in the Molecular Genetics Core Facility at Children’s Hospital Boston, supported by NIH P30 HD 18655 through the Intellectual and Developmental Disabilities Research Center (IDDRC) and NIH P50 NS40828 through the Neuromuscular Disease Project.


  • MEGF10
  • Myopathy
  • Tyrosine phosphorylation


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