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Cysteine mutations cause defective tyrosine phosphorylation in MEGF10 myopathy
Author(s) -
Mitsuhashi Satomi,
Mitsuhashi Hiroaki,
Alexander Matthew S.,
Sugimoto Hiroyuki,
Kang Peter B.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.002
Subject(s) - phosphorylation , tyrosine phosphorylation , tyrosine , biology , microbiology and biotechnology , myopathy , mutation , phosphorylation cascade , signal transduction , cancer research , protein phosphorylation , biochemistry , genetics , gene , protein kinase a
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.