A phosphorylated variant of the mast/stem cell growth factor receptor KIT is upregulated in dorsal root ganglia of Friedreich ataxia.

Friedreich ataxia (FA) causes hypoplasia of nerve cells in dorsal root ganglia (DRG). Beyond hypoplasia, however, the lesion in DRG includes disorganization and proliferation of satellite cells, formation of residual nodules, and neuronophagia. Antibody microarray analyses of DRG lysates with 878 validated antibodies that target cell signaling proteins reveal prominent up-regulation of the mast/stem cell growth factor (SCF) receptor-tyrosine kinase KIT. In its bioactive form upon engagement with SCF, KIT undergoes dimerization and autophosphorylation at Tyr-936 amongst other sites, and is hereafter called KIT-pY936. By immunohistochemistry and double-label laser scanning confocal immunofluorescence, KIT-pY936 is located in satellite cell cytoplasm. Electrophoresis and Western blots of DRG lysates show that the strong immunoreactivity of KIT-pY936 is due to a new truncated KIT variant of 50 kDa. KIT is a proto-oncogenic protein with prominent roles in hematopoiesis including mast cell proliferation. In conclusion, proteomic analysis confirms the prominent participation of a new truncated KIT in satellite cells in the pathogenesis of FA in DRG.