Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy

FEBS Lett. 2013 Sep 17;587(18):2952-7. doi: 10.1016/j.febslet.2013.08.002. Epub 2013 Aug 15.

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.

Keywords: MEGF10; Myopathy; Tyrosine phosphorylation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Motifs
  • Animals
  • Binding Sites
  • CSK Tyrosine-Protein Kinase
  • Cell Line
  • Cell Proliferation
  • Cysteine / genetics
  • Cysteine / metabolism*
  • Gene Expression Regulation
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Mice
  • Molecular Sequence Data
  • Muscular Diseases / genetics
  • Mutation*
  • Myoblasts / metabolism*
  • Myoblasts / pathology
  • Phosphorylation
  • Protein Binding
  • Protein Interaction Domains and Motifs
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Signal Transduction
  • Tyrosine / genetics
  • Tyrosine / metabolism*
  • src-Family Kinases / genetics
  • src-Family Kinases / metabolism*

Substances

  • Megf10 protein, mouse
  • Membrane Proteins
  • Tyrosine
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human
  • Cysteine