A-BETA PEPTIDE ENHANCES FOCAL ADHESION KINASE FYN ASSOCIATION IN A RAT CNS NERVE-CELL LINE

Neurotoxicity of the amyloid beta protein (A beta) is known to correla te with a selective change in protein tyrosine phosphorylation (Tyr(P) ) of focal adhesion kinase (FAK) (Zhang et al., J. Biol. Chem., 269 (1 994) 25247-25250). The current work has found that exposure of neurona l cells to A beta upregulates the stable association of FAK with Fyn, a neuronally-enriched protein tyrosine kinase of the Src-family. In ce lls incubated with aged A beta 1-42, the amount of immunoprecipitable FAK-Fyn complex increased similar to 280%. Equivalent results were obt ained whether anti-FAK or anti-Fyn was used to precipitate the complex . Cells incubated with non-toxic A beta 17-42, which makes aggregates and attaches to cells but does not upregulate FAK Tyr(P), exhibited no increase in FAK-Fyn complex. Aberrant Fyn activity due to the A beta- evoked association with FAK could play a role in neuronal degeneration and also cause anomalies in synaptic plasticity. These possibilities are of particular significance because of the reported increase in Fyn immunoreactivity in Alzheimer's-afflicted neurons (Shirazi and Wood, NeuroReport, 4 (1993) 435-437).