Decreased insulin-like growth factor I-mediated protein tyrosine phosphorylation in human olivopontocerebellar atrophy and lurcher mutant mouse.
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.
Vig
P J
PJ
Department of Neurology, University of Mississippi Medical Center, Jackson 39216.
Desaiah
D
D
Joshi
P
P
Subramony
S H
SH
Fratkin
J D
JD
Currier
R D
RD
D000595:Amino Acid Sequence; D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007457:Iodine Radioisotopes; D008297:Male; D051379:Mice; D008818:Mice, Neurologic Mutants; D008969:Molecular Sequence Data; D009410:Nerve Degeneration / Q000502:physiology; D009849:Olivopontocerebellar Atrophies / Q000201:enzymology / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology
D007457:Iodine Radioisotopes; D010455:Peptides; D007334:Insulin-Like Growth Factor I; D011505:Protein-Tyrosine Kinases; D017526:Receptor, IGF Type 1