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 correlate with a selective change in protein tyrosine phosphorylation (Tyr(P)) of focal adhesion kinase (FAK) (Zhang et al., J. Biol. Chem., 269 (1994) 25247-25250). The current work has found that exposure of neuronal cells to A beta upregulates the stable association of FAK with Fyn, a neuronally-enriched protein tyrosine kinase of the Src-family. In cells incubated with aged A beta 1-42, the amount of immunoprecipitable FAK-Fyn complex increased approximately 280%. Equivalent results were obtained 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).
Zhang
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Department of Neurobiology and Physiology, Northwestern University, Evanston, IL 60208, USA.
Qiu
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HE
Krafft
G A
GA
Klein
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WL
D016564:Amyloid beta-Protein Precursor / Q000633:toxicity*; D000818:Animals; D015815:Cell Adhesion Molecules / Q000187:drug effects*; D002460:Cell Line / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects*; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000187:drug effects*; D051381:Rats
D016564:Amyloid beta-Protein Precursor; D015815:Cell Adhesion Molecules; D011505:Protein-Tyrosine Kinases; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496052:Ptk2 protein, rat