Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy.

Academic Article

Abstract

  • 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.
  • Published In

  • FEBS Letters  Journal
  • Keywords

  • MEGF10, Myopathy, Tyrosine phosphorylation, Amino Acid Motifs, Animals, Binding Sites, Cell Line, Cell Proliferation, Cysteine, Gene Expression Regulation, Membrane Proteins, Mice, Molecular Sequence Data, Muscular Diseases, Mutation, Myoblasts, Phosphorylation, Protein Binding, Protein Interaction Domains and Motifs, Sequence Alignment, Sequence Homology, Amino Acid, Signal Transduction, Tyrosine, src-Family Kinases
  • Digital Object Identifier (doi)

    Authorlist

  • Mitsuhashi S; Mitsuhashi H; Alexander MS; Sugimoto H; Kang PB
  • Start Page

  • 2952
  • End Page

  • 2957
  • Volume

  • 587
  • Issue

  • 18