Decreased insulin-like growth factor I-mediated protein tyrosine phosphorylation in human olivopontocerebellar atrophy and lurcher mutant mouse

J Neurol Sci. 1994 Jun;124(1):38-44. doi: 10.1016/0022-510x(94)90008-6.


We examined insulin-like growth factor I (IGF-I)-dependent phosphorylation and protein tyrosine kinase (PTK) activity in cerebellar cortex of normal humans, patients with olivopontocerebellar atrophy (OPCA) ("C" kindred) and in lurcher mutant mouse, a suggested animal model for OPCA. PTK activity and IGF-I-dependent protein tyrosine phosphorylation was significantly reduced in cerebellar cortex of human OPCA patients as compared to the normal controls. Immunoblot analysis also demonstrated a decrease in cerebellar 80 kDa phosphotyrosine protein in these patients. By autoradiography, IGF-I receptors were localized in the molecular layer of 30-day-old control and lurcher mutant mice cerebella. However, the lurcher mutant mice showed a decrease in [125I]-IGF-I binding in the molecular layer as compared to the littermate controls. The IGF-I receptor autophosphorylation was also markedly reduced in 15-day- and 22-day-old lurcher cerebella. These results suggest that the process of cerebellar degeneration in human OPCA and lurcher mutant mouse may be associated with altered IGF-I receptor binding and protein tyrosine phosphorylation.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Autoradiography
  • Blotting, Western
  • Cell Membrane / metabolism
  • Female
  • Insulin-Like Growth Factor I / physiology*
  • Iodine Radioisotopes
  • Male
  • Mice
  • Mice, Neurologic Mutants
  • Molecular Sequence Data
  • Nerve Degeneration / physiology
  • Olivopontocerebellar Atrophies / enzymology
  • Olivopontocerebellar Atrophies / metabolism*
  • Peptides / metabolism
  • Phosphorylation
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor, IGF Type 1 / metabolism
  • Signal Transduction / physiology


  • Iodine Radioisotopes
  • Peptides
  • Insulin-Like Growth Factor I
  • Protein-Tyrosine Kinases
  • Receptor, IGF Type 1